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ABSTRACT: Members of the Orai family are highly selective calcium ion channels that play an important role in store-operated calcium entry. Among the three known Orai isoforms, Orai3 has gained increased attention, notably for its emerging role in cancer. We recently demonstrated that Orai3 channels are over-expressed in breast cancer (BC) biopsies, and involved specifically in proliferation, cell cycle progression and survival of MCF-7 BC cells. Here, we investigate the downstream signaling mechanisms affected by Orai3 silencing, leading to the subsequent functional impact specifically seen in MCF-7 cancer cells. We report a correlation between Orai3 and c-myc expression in tumor tissues and in the MCF-7 cancer cell line by demonstrating that Orai3 down-regulation reduces both expression and activity of the proto-oncogene c-myc. This is likely mediated through the MAP Kinase pathway, as we observed decreased pERK1/2 levels and cell-cycle arrest in G1 phase after Orai3 silencing. Our results provide strong evidence that the c-myc proto-oncogene is influenced by the store-operated calcium entry channel Orai3 through the MAP Kinase pathway. This connection provides new clues in the downstream mechanism linking Orai3 channels and proliferation, cell cycle progression and survival of MCF-7 BC cells.
Biochimica et Biophysica Acta 12/2012; · 4.66 Impact Factor
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ABSTRACT: Breast cancer is the most frequently occurring cancer in women and has the highest rate of mortality. Ion channels such as the transient receptor potential (TRP) channels could play a critical role in the development and progression of cancer. Although these channels are frequently and abundantly expressed in many tumors, their expression, activity, and roles in the context of breast cancer remain poorly understood. This review summarizes our current knowledge regarding TRP channels expressed in human breast tissue, primary human breast epithelial cells, and cell lines, the functional role of TRP channels during breast cancer cell growth and migration, as well as their relationship with clinical and pathological features.
Trends in Molecular Medicine 12/2012; · 10.35 Impact Factor
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ABSTRACT: Breast cancer (BC) has the highest incidence rate in women in industrialized countries. Statistically, it is estimated that one out of 10 women will develop BC during her life. Evidence is accumulating for the role of ion channels in the development of cancer. Most studied ion channels in BC are K(+) channels, which are involved in cell proliferation, cell cycle progression and cell migration, and Na(+) channels, which correlate with invasiveness. Emerging studies demonstrated the role of Ca(2+) signaling in cancer cell proliferation, survival and migration. Recent findings demonstrated that the expression and/or activity of the transient receptor potential (TRP) channels are altered in several cancers. Among the TRP families, TRPC (canonical or classical), TRPM (melastatin) and TRPV (vanilloid) are related to malignant growth and cancer progression. Although these channels are frequently and abundantly expressed in many tumors, their specific expression, activity and roles in BC are still poorly understood. The expression of TRP channels has also been proposed as a tool for diagnosis, prognosis and/or therapeutic issues of several diseases. In cancer, TRPV6 and TRPM8 have been proposed as tumor progression markers of prostate cancer outcome and TRPC6 as a novel therapeutic target for esophageal carcinoma. Interestingly high levels of TRPC3 expression correlate with a favorable prognosis in patients with lung adenocarcinoma. Our team has recently reported the expression and role of TRPC1, TRPC6, TRPM7, TRPM8 and TRPV6 in BC cell lines and primary cultures. We have also investigated TRP expression and their clinical significance in human breast adenocarcinoma and we suggest that TRP channels are new potential BC markers. Indeed TRPC1 and TRPM8 may be considered as good prognosis markers of well-differentiated tumors, TRPM7 as a proliferative marker of poorly differentiated tumors and TRPV6 as a prognosis marker of aggressive cancers. In this review, we summarize the data reported to date regarding the changes in TRP expression associated with BC. We also discuss the importance of TRP channels in BC cells proliferation and migration and their interest as new BC markers.
Bulletin du cancer 05/2012; 99(6):655-64. · 0.67 Impact Factor
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ABSTRACT: Breast cancer (BC) has a poor prognosis due to its strong metastatic ability. Accumulating data present ether à go-go (hEag1) K(+) channels as relevant player in controlling cell cycle and proliferation of non-invasive BC cells. However, the role of hEag1 in invasive BC cells migration is still unknown. In this study, we studied both the functional expression and the involvement in cell migration of hEag1 in the highly metastatic MDA-MB-231 human BC cells. We showed that hEag1 mRNA and proteins were expressed in human invasive ductal carcinoma tissues and BC cell lines. Functional activity of hEag1 channels in MDA-MB-231 cells was confirmed using astemizole, a hEag1 blocker, or siRNA. Blocking or silencing hEag1 depolarized the membrane potential and reduced both Ca(2+) entry and MDA-MB-231 cell migration without affecting cell proliferation. Recent studies have reported that Ca(2+) entry through Orai1 channels is required for MDA-MB-231 cell migration. Down-regulation of hEag1 or Orai1 reduced Ca(2+) influx and cell migration with similar efficiency. Interestingly, no additive effects on Ca(2+) influx or cell migration were observed in cells co-transfected with sihEag1 and siOrai1. Finally, both Orai1 and hEag1 are expressed in invasive breast adenocarcinoma tissues and invaded metastatic lymph node samples (LNM(+)). In conclusion, this study is the first to demonstrate that hEag1 channels are involved in the serum-induced migration of BC cells by controlling the Ca(2+) entry through Orai1 channels. hEag1 may therefore represent a potential target for the suppression of BC cell migration, and thus prevention of metastasis development.
Journal of Cellular Physiology 04/2012; 227(12):3837-46. · 3.87 Impact Factor
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ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of cancer with a tendency to invade surrounding healthy tissues, leading to a largely incurable disease. Despite many advances in modern medicine, there is still a lack of early biomarkers as well as efficient therapeutical strategies. The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel that is involved in maintaining Ca(2+) and Mg(2+) homeostasis. It has been recently reported to regulate cell differentiation, proliferation and migration. However, the role of TRPM7 in PDAC progression is far to be understood. In our study, we show that TRPM7 is 13-fold overexpressed in cancer tissues compared to the healthy ones. Furthermore, TRPM7 staining is stronger in tumors with high grade, suggesting a correlation between TRPM7 expression and PDAC progression. Importantly, TRPM7 expression is inversely related to patient survival. In BxPC-3 cell line, dialyzing the cytoplasm during the patch-clamp whole-cell recording with a 0-Mg(2+) solution activated a nonselective current with a strong outward rectification. This cation current is inhibited by intracellular Mg(2+) and by TRPM7 silencing. The downregulation of TRPM7 by small interference RNA dramatically inhibited intracellular Mg(2+) fluorescence and cell migration without affecting cell proliferation, suggesting that TRPM7 contributes to Mg(2+) entry and cell migration. Moreover, external Mg(2+) following TRPM7 silencing fully restored the cell migration. In summary, our results indicate that TRPM7 is involved in the BxPC-3 cell migration via a Mg(2+)-dependent mechanism and may be a potential biomarker of poor prognosis of PDAC.
International Journal of Cancer 02/2012; 131(6):E851-61. · 5.44 Impact Factor
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ABSTRACT: To assess the usefulness of histopathologic examination in forensic autopsies.
All consecutive pathological reports and slides from forensic autopsies performed in our department since 2006 have been reviewed.
Four hundred forensic necropsies were reviewed. In only 150 cases (38%), pathologists had data about manner of death and gross autopsy findings. Major diagnoses, related to death, and unsuspected by forensic pathologists, were discovered in 83 cases (21%): in 48 cases (12%) gross examination of the heart, lungs and liver showed gross diagnoses missed by the forensic pathologists, and in only 35 cases (9%) microscopic examination revealed a major unsuspected diagnosis (in brain, heart, lungs, liver, kidney and pancreas specimens). In 213 cases (53%), histopathologic examination confirmed gross autopsy findings and allowed to date some wounds. In 104 cases (26%), microscopic examination was not contributory.
Microscopic examination revealed major diagnoses in less than 10% of forensic autopsies. Its effectiveness is limited for homicides and suicides. Systematic microscopic examination of numerous organs is often useless and should be limited to cases with no anatomic causes of death. Our study emphasizes the need for a better communication between forensic pathologists and histopathologists, and for a better training of some forensic pathologists for gross examination.
Annales de Pathologie 02/2012; 32(1):4-13. · 0.25 Impact Factor
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ABSTRACT: Breast cancer (BC) is the leading cancer in the world in terms of incidence and mortality in women. However, the mechanism by which BC develops remains largely unknown. The increase in cytosolic free Ca(2+) can result in different physiological changes including cell growth and death. Orai isoforms are highly Ca(2+) selective channels. In the present study, we analyzed Orai3 expression in normal and cancerous breast tissue samples, and its role in MCF-7 BC and normal MCF-10A mammary epithelial cell lines. We found that the expression of Orai3 mRNAs was higher in BC tissues and MCF-7 cells than in normal tissues and MCF-10A cells. Down-regulation of Orai3 by siRNA inhibited MCF-7 cell proliferation and arrested cell cycle at G1 phase. This phenomenon is associated with a reduction in CDKs 4/2 (cyclin-dependent kinases) and cyclins E and D1 expression and an accumulation of p21(Waf1/Cip1) (a cyclin-dependent kinase inhibitor) and p53 (a tumor-suppressing protein). Orai3 was also involved in MCF-7 cell survival. Furthermore, Orai3 mediated Ca(2+) entry and contributed to intracellular calcium concentration ([Ca(2+)](i)). In MCF-10A cells, silencing Orai3 failed to modify [Ca(2+)](i), cell proliferation, cell-cycle progression, cyclins (D1, E), CDKs (4, 2), and p21(Waf1/Cip1) expression. Our results provide strong evidence for a significant effect of Orai3 on BC cell growth in vitro and show that this effect is associated with the induction of cell cycle and apoptosis resistance. Our study highlights a possible role of Orai3 as therapeutic target in BC therapy.
Journal of Cellular Physiology 02/2011; 226(2):542-51. · 3.87 Impact Factor
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ABSTRACT: Transient Receptor Potential (TRP) channels are expressed in many solid tumors. However, their expression in breast cancer remains largely unknown. Here, we investigated the profile expression of 13 TRP channels in human breast ductal adenocarcinoma (hBDA) and performed a correlation between their overexpression and pathological parameters.
The TRP channels expression was determined by RT-PCR in hBDA tissue, in human breast cancer epithelial (hBCE) primary culture and in MCF-7 cell line. The TRP protein level was evaluated by immunohistochemistry in hBDA tissue samples of 59 patients.
TRPC1, TRPC6, TRPM7, TRPM8, and TRPV6 channels were overexpressed in hBDA compared to the adjacent non-tumoral tissue. Most interestingly, TRPC1, TRPM7 and TRPM8 expression strongly correlated with proliferative parameters (SBR grade, Ki67 proliferation index, and tumor size), and TRPV6 was mainly overexpressed in the invasive breast cancer cells. Using laser capture microdissection, we found that TRPV6 expression was higher in invasive areas, compared to the corresponding non-invasive ones. Moreover, TRPV6 silencing inhibited MDA-MB-231 migration and invasion, and MCF-7 migration.
TRP channels are aberrantly expressed in hBDA, hBCE primary cultures, and cell lines, and associated with pathological parameters. The high expression of TRP channels in tumors suggests the potential of these channels for diagnostic, prognosis and/or therapeutic approaches in human breast ductal adenocarcinoma.
Cellular Physiology and Biochemistry 01/2011; 28(5):813-22. · 2.86 Impact Factor
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ABSTRACT: To study the composition of foodstuffs (sausage, merguez, chipolata) on microscopic examination.
Six sausages, merguez, and chipolatas, sold in supermarkets were studied. The samples were weighed before and after dehydration to assess the water composition. Foodstuffs specimens were formalin-fixed, paraffin-embedded and analyzed on microscopic examination. Proportions of different tissues were assessed by morphometric analysis.
Specimens contained a high proportion of water (40 to 55%). Striated muscular fibers represented from 0.7 to 15.3% for the sausages and the merguez, and from 61 to 76.5% for the chipolatas. Sausages and merguez contained from 43.3 to 49.2% of adipose tissue. All the specimens had fibrous tissue and most of them had small fragments of bone and cartilaginous tissue. Fragments of salivar glands were found in the sausages and fragments of lymphoid tissue were found in merguez. There were neither parasite nor brain tissue. Manufacturer wrote on the label the presence of "meat" with no information about the nature and the proportion of tissues in the foodstuffs specimens. Prices of the foodstuffs were globally correlated to the quantity of muscular fibers in the specimens.
Pathological studies are not performed in France for the control of foodstuffs. Microscopic analysis could be interesting, as well as biochemical and bacteriological studies, in order to identify the nature and the proportion of tissues involved in the composition of the foodstuffs, to search tissues with potential risk of pathogenic agents transmission, and to search for some parasites.
Annales de Pathologie 10/2010; 30(5):344-9. · 0.25 Impact Factor
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ABSTRACT: K+ channels are key molecules in the progression of several cancer types and are considered to be potential targets for cancer therapy. In this study, we investigated the intermediate- conductance Ca2+-activated K+ channels (hKCa3.1) expression in both breast carcinoma (BC) specimens and human breast cancer epithelial primary cell cultures (hBCE) using immuno-histochemistry (60 samples), quantitative Real-Time RT-PCR (30 samples) and Western blot assay (30 samples). We also looked at whether or not the expression of these channels is correlated with breast carcinomas grade tumours and metastasis status. Furthermore, we characterized the hKCa3.1 channel activity in hBCE cells by using the Whole Cell Patch Clamp Technique. We found that hKCa3.1 transcripts and proteins were expressed in both BC samples and hBCE cells. Clinicopathologic evaluation indicated a significant correlation between hKCa3.1-expression and tumour grade. hKCa3.1 mRNA and protein were more highly expressed in grade III tumours than in both grades I and II. However, the hKCa3.1 expression-increase according to grade was only observed in tumours with negative metastasis status. Moreover, the hKCa3.1 channels expressed in hBCE cells are functional. This was attested by patch-clamp recordings showing typical hKCa3.1-mediated currents in these cells. In conclusion, these data suggest that hKCa3.1 might contribute to breast tumour-progression and can serve as a useful prognostic marker for breast cancer.
Histology and histopathology 10/2010; 25(10):1247-55. · 2.48 Impact Factor
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ABSTRACT: To investigate the association between benfluorex use and organic restrictive mitral regurgitation (MR) in patients admitted to hospital for diagnostic work-up of MR of unclear aetiology.
Among patients referred between 2003 and 2008 to our tertiary centre for diagnostic work-up of MR, we retrospectively identified 22 consecutive patients (65 +/- 12 years, 64% women) with restrictive organic MR of unclear aetiology. Using propensity scores, 22 out of 156 patients who underwent surgery for dystrophic MR due to flail leaflets during the same time period were matched for age, sex, height, body weight, and diabetes with the study population. Eight of the 22 patients with restrictive organic MR of unclear aetiology (36.4%) had a history of benfluorex use, and in one patient (4.5%) we identified previous exposure to both benfluorex and fenfluramine. The frequency of benfluorex treatment in patients with restrictive organic MR of unclear aetiology was significantly higher compared with that observed in the dystrophic MR group (36.4 vs. 4.5%; P-value 0.039). Patients with restrictive MR treated with benfluorex (body mass index 31 +/- 6 kg/m(2)) were all dyslipidaemic and 67% had diabetes. Echocardiography identified moderate or severe restrictive organic MR in all cases. Median total duration of benfluorex therapy was 63(12-175) months, at a daily dose of 450 (300-450) mg, leading to a cumulative dose of 850 (108-2363) g.
Although it cannot affirm a definitive causal relationship, the present study strongly suggests that patients treated with benfluorex might incur a risk of restrictive organic valvular heart disease. Therefore, echocardiography should be performed in patients exposed to benfluorex in case of occurrence of symptoms or signs of valvular disease. Further data are needed to confirm these findings.
European Heart Journal – Cardiovascular Imaging 03/2010; 11(7):614-21. · 2.32 Impact Factor
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ABSTRACT: For several years, a new population of microglia derived from bone marrow has been described in multiple settings such as infection, trauma, and neurodegenerative disease. The aim of this study was to investigate the migration of bone marrow-derived cells to the brain parenchyma after stress exposure. Stress exposure was performed in mice that had received bone marrow transplantation from GFP mice, allowing identification of blood-derived elements within the brain. Electric foot-shock exposure was chosen because of its ability to serve as fundamental and physical stress in mice. Bone marrow-derived GFP(+) cells migrated to the ventral part of the hippocampus and acquired a ramified microglia-like morphology. Microglia marker Iba1 was expressed by 100% of the ramified cells, whereas ramified cells were negative for the astrocyte marker GFAP. Compared with the case in the control group, ramified cells significantly increased after chronic exposure to stress (5 days). One month after 5 days of stress exposure, ramified cells significantly decreased in ventral hippocampus compared with the group examined immediately after the last stress exposure. We report for the first time the migration of bone marrow-derived cells to the ventral hippocampus after stress exposure. These cells have the characteristics of microglia. Mechanisms responsible for this migration and their roles in the brain remain to be determined.
Journal of Neuroscience Research 02/2010; 88(9):1890-7. · 2.74 Impact Factor
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ABSTRACT: The calcium-permeable cation channel TRPM8 (melastatin-related transient receptor potential member 8) is over-expressed in several cancers. The present study aimed at investigating the expression, function and potential regulation of TRPM8 channels by ER alpha (estrogen receptor alpha) in breast cancer.
RT-PCR, Western blot, immuno-histochemical, and siRNA techniques were used to investigate TRPM8 expression, its regulation by estrogen receptors, and its expression in breast tissue. To investigate the channel activity in MCF-7 cells, we used the whole cell patch clamp and the calcium imaging techniques.
TRPM8 channels are expressed at both mRNA and protein levels in the breast cancer cell line MCF-7. Bath application of the potent TRPM8 agonist Icilin (20 microM) induced a strong outwardly rectifying current at depolarizing potentials, which is associated with an elevation of cytosolic calcium concentration, consistent with established TRPM8 channel properties. RT-PCR experiments revealed a decrease in TRPM8 mRNA expression following steroid deprivation for 48 and 72 hours. In steroid deprived medium, addition of 17-beta-estradiol (E2, 10 nM) increased both TRPM8 mRNA expression and the number of cells which respond to Icilin, but failed to affect the Ca2+ entry amplitude. Moreover, silencing ERalpha mRNA expression with small interfering RNA reduced the expression of TRPM8. Immuno-histochemical examination of the expression of TRPM8 channels in human breast tissues revealed an over-expression of TRPM8 in breast adenocarcinomas, which is correlated with estrogen receptor positive (ER+) status of the tumours.
Taken together, these results show that TRPM8 channels are expressed and functional in breast cancer and that their expression is regulated by ER alpha.
BMC Cancer 01/2010; 10:212. · 3.01 Impact Factor
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ABSTRACT: Anogenital mammary-like glands (MLGs) are a normal constituent of the anogenital area showing similarities to breast glands. MLGs are recognized to be the possible origin for various neoplastic and reactive conditions that show homology to their mammary counterparts. We report the case of an 85-year-old woman presenting with 10 cm polypoid mass of the perianal region. Histopathological examination of the excised lesion showed atypical apocrine proliferation arising in a complex lesion with features of fibroadenoma, adenosis and hyperplastic and cystic change. Normal MLGs were observed at the tumor periphery. There was no recurrence after 3 years of follow up. This report represents an illustration of the complexity of lesions developed from MLG.
Journal of Cutaneous Pathology 10/2009; 36 Suppl 1:52-5. · 1.56 Impact Factor
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ABSTRACT: The aim of our survey was to assess the perception of teaching pathology by the medical students in the sixth year of the medical course (DCEM4), in the faculty of medicine of Amiens.
Just after an exam in December 2008, an anonymous questionnaire of 19 items, dealing with pathology, the teaching of pathology and tutorials, was given to the 127 medical students in DCEM4.
Seventy-four percent of the students out of the 127 students filled and gave back the questionnaire (response rate: 58%). Eighty-nine percent of the students considered their knowledge in pathology inadequate. Fifty-three percent of the students considered the teaching of pathology mediocre. For 85% of the students, tutorials were useful. For 93% of the students pathology plays a main role in modern medicine. Thirty-eight percent of the students considered that pathology was an interesting specialty. Sixty-nine percent of them did not know how a department of pathology functioned. Four percent of the students would like to choose a training in pathology.
Although the results are not available for all French faculties of medicine, this survey underlines the present limits of the teaching of pathology, which is not coming up to the students' expectations. The students appreciate tutorials but pathology is not attractive. More lectures about pathology after the third year of the medical course, a better communication and the reception of more medical students in the departments of pathology could improve the situation.
Annales de Pathologie 07/2009; 29(3):173-9. · 0.25 Impact Factor
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ABSTRACT: Because transient receptor potential (TRP) channels have been implicated in tumor progression, we have investigated the potential role of TRPM7 channel in breast cancer cell proliferation. Under whole cell patch clamp, a Mg(2+)-inhibited cationic (MIC) current was observed in MCF-7 cells. This current was characterized by an inward current and a strong outward rectifying current that were both inhibited in a concentration-dependent manner by the presence of intracellular Mg(2+) or Mg(2+)-ATP. The inward current was reduced by La(3+), and the outward current was sensitive to 2-aminoethoxydiphenyl borate (2-APB), spermine, La(3+), and flufenamic acid. Importantly, a similar MIC current was also recorded in the primary culture of human breast cancerous epithelial cells (hBCE). Moreover, TRPM7 transcripts were found in both hBCE and MCF-7 cells. In MCF-7 cells, the MIC current was inhibited by TRPM7 small interfering RNA. Interestingly, we found that cell proliferation and intracellular Ca(2+) concentration were also reduced by TRPM7 silencing in MCF-7 cells. TRPM7 channels were also found in both human breast cancer and healthy tissues. Importantly, TRPM7 channel was overexpressed in grade III breast cancer samples associated with important Ki67 or tumor size. Our findings strongly suggest that TRPM7 is involved in the proliferative potentiality of breast cancer cells, probably by regulating Ca(2+) influx.
AJP Cell Physiology 07/2009; 297(3):C493-502. · 3.54 Impact Factor
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ABSTRACT: The aim of this study was to examine expression of 2 potassium (K) channels in pancreatic adenocarcinoma.
The immunohistochemical and mRNA expression of GIRK1 (G-protein inwardly rectifying K channel 1) and KV1.3 channel (voltage-dependent K channel) was studied in 55 and 18 adenocarcinomas and 33 and 8 normal pancreas specimens, respectively. The methylation status of KV1.3 promoter was studied by methyl-specific polymerase chain reaction in 33 pancreatic adenocarcinomas. The results were correlated with the patients' prognosis.
GIRK1 was highly expressed in 80% (44/55) of adenocarcinoma samples versus 57.6% (19/33) of normal samples (P=0.03), as confirmed by reverse transcriptase-polymerase chain reaction results (P=0.007). KV1.3 expression was decreased in pancreatic adenocarcinomas compared with normal tissue (7.3% vs 39.4%; P=0.0005). KV1.3 down-expression was associated with metastatic tumors (P=0.018). KV1.3 promoter methylation was observed in 69.7% (22/33) of adenocarcinomas.
This is the first report of deregulation of 2 K channels in pancreatic adenocarcinoma. GIRK1 was highly expressed in pancreatic adenocarcinomas, corresponding to its role in cell proliferation. Methylation of KV1.3 gene promoter could explain the decrease of KV1.3 expression in adenocarcinomas. New therapeutic agents, such as DNA methylation inhibitors, could be useful against this dramatic cancer.
Pancreas 06/2009; 38(6):649-54. · 2.39 Impact Factor
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La Presse Médicale 05/2009; 38(9):1370-4. · 0.67 Impact Factor
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Histopathology 03/2009; 54(3):388-91. · 3.08 Impact Factor
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ABSTRACT: DNA methylation is an important mechanism for gene silencing and has already been described for several genes in breast cancer. A previous immunohistochemistry study demonstrated a decrease of K(v)1.3 potassium channel expression in breast adenocarcinoma compared to normal breast tissue.
Methyl-specific PCR (MSP), immunohistochemistry and RNA extraction were performed on breast adenocarcinoma. MSP and DNA extraction were also performed on one breast carcinoma cell line and on primary culture normal cells.
DNA methylation of K(v)1.3 gene promoter was observed in 42.3% of samples (22/52). The methylated status was associated with poorly differentiated tumors (p=0.04) and younger patients (p=0.048). Decreased K(v)1.3 expression was observed in grade III tumors, at both the mRNA and protein levels, while methylation increased in grade III tumors. Finally, K(v)1.3 gene promoter was methylated in the MCF-7 breast carcinoma cell line while promoter methylation was absent in primary culture of normal breast cells (HMEpC).
We report, for the first time, the methylation of the K(v)1.3 gene promoter in breast adenocarcinoma. Our data suggest that DNA methylation is responsible for a decrease of K(v)1.3 gene expression in breast adenocarcinoma and is associated with poorly differentiated tumors and younger patients.
Cellular Physiology and Biochemistry 02/2009; 24(1-2):25-32. · 2.86 Impact Factor
