[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this study was to investigate possible mechanisms of LOX gene effects on invasion and metastasis of breast cancer cells by RNA interference.
LOX-RNAi-LV was designed, synthesized, and then transfected into a breast cancer cell line (MDA-MB-231). Expression of LOX, MMP-2 and MMP-9 was determined by real-time PCR, and protein expression of LOX by Western blotting. Cell migration and invasiveness were assessed with Transwell chambers. A total of 111 cases of breast cancer tissues, cancer-adjacent normal breast tissues, and 20 cases of benign lesion tissues were assessed by immunohistochemistry.
Expression of LOX mRNA and protein was suppressed, and the expression of MMP-2 and MMP-9 was significantly lower in the RNAi group than the control group (P<0.05), after LOX-RNAi-LV was transfection into MDA-MB-231 cells. Migration and invasion abilities were obviously inhibited. The expression of LOX protein in breast cancer, cancer-adjacent normal breast tissues and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20), respectively, associations being noted with clinical stage, lymph node metastasis, tumor size and ER, PR, HER2, but not age. LOX protein was positively correlated with MMP-2 and MMP-9.
LOX displayed an important role in invasion and metastasis of breast cancer by regulating MMP-2 and MMP-9 expression which probably exerted synergistic effects on the extracellular matrix (ECM).
Asian Pacific journal of cancer prevention: APJCP 07/2012; 13(7):3507-11. DOI:10.7314/APJCP.2012.13.7.3507 · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate possible mechanism of silencing lysyl oxidase (LOX) gene by RNA interference affecting on invasion and metastasis of breast cancer cells.
LOX-RNAi-LV was designed and synthesized, which was transfected into breast cancer cell line MDA-MB-231. The expressions of LOX, MMP-2 and MMP-9 were determined by Real-time PCR in MDA-MB-231 cells, and the protein expression of LOX was determined by Western blot. The cells migration and invasion abilities were measured by cell migration and invasion test. 111 cases of breast cancer tissue and cancer-adjacent breast tissues and 20 cases of benign lesion tissues of LOX, MMP-2 and MMP-9 were detected by immunohistochemistry, and the relationship of LOX and clinicopathological characteristics was analyzed.
The expression levels of LOX mRNA and protein were down-regulated obviously after transfecting LOX-RNAi-LV, with the inhibition rate 89.2% ± 1.3% and 84.4% ± 0.4% repectively. The relative expressions of MMP-2 and MMP-9 mRNA were 0.496 ± 0.021 and 0.571 ± 0.099 in RNAi group, which was significantly lower than that in negative control group (0.846 ± 0.047, 0.786 ± 0.042) and blank control group (1.000 ± 0.000, 1.000 ± 0.000) (both P < 0.05). Cell migration and invasion test showed the average cell numbers per field in the group RNAi were 47 ± 2 and 63 ± 2, was significantly lower than that in negative control group (100 ± 1, 118 ± 2) and blank control group (100 ± 1, 118 ± 2) (both P < 0.05). The expression of LOX protein in breast cancer, cancer-adjacent breast tissues and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20), the expression of LOX protein in breast cancer was significantly higher than that in cancer-adjacent breast tissues and benign lesion tissues (P = 0.019). The expression of LOX protein was associated with clinical stage, lymph node metastasis, tumor size. Correlation analysis showed that LOX protein expression was significantly positive correlation with MMP-2 (r = 0.262, P = 0.005) and MMP-9 (r = 0.424, P = 0.000).
LOX can promote invasion and metastasis of breast cancer; LOX and MMP-2, MMP-9 may have a synergistic role in promoting invasion and metastasis of breast cancer.
Zhonghua yi xue za zhi 05/2012; 92(20):1379-83. DOI:10.3760/cma.j.issn.0376-2491.2012.20.005
[Show abstract][Hide abstract] ABSTRACT: To study the expression and clinical significance of ribosomal S6 kinase-4 (RSK-4) in breast cancer and explore the role of RSK-4 in the genesis and development of breast cancer.
The expression levels of RSK-4 mRNA and protein were detected in 56 cases of breast cancer and the normal breast tissues, as well as in 20 cases of breast benign lesions, by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry.
The expression rates of RSK-4 mRNA in breast cancer, the normal breast tissues and breast benign lesions were 48.2%, 76.8% and 75.0%, respectively. The expression level of RSK-4 mRNA in breast cancer was significantly lower than those in normal breast tissues and breast benign lesions tissues (P < 0.05). The expression level of RSK-4 significantly correlated with tumor size and clinical stage (P < 0.05).The expression rate of RSK-4 protein was 39.3% in breast cancer tissues, which was significantly lower than that of normal breast tissues (71.4%) and breast benign lesions (75.0%, P < 0.01). The expression level of RSK-4 protein was lower in breast cancer with large tumor, high clinical stage and lymph node metastasis. In 56 cases of breast cancer samples, the consistency rate of RSK-4 mRNA and protein was 73.2%. A significant correlation was found between RSK-4 mRNA and protein (χ² = 10.254, P < 0.05).
The down-regulation of RSK-4 expression in breast caner suggests that it is a breast cancer suppressor gene, and the lack or down-regulation of RSK-4 expression is involved in the genesis and progression of breast cancer.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 06/2011; 33(6):452-6.
[Show abstract][Hide abstract] ABSTRACT: ObjectiveThe aim of the present study is to explore the expression of a specific marker of breast cancer, small breast epithelial mucin
(SBEM) mRNA, in peripheral blood and to investigate its significance.
MethodsThe expressions of SBEM-mRNA in peripheral blood of 67 patients with breast cancer, 16 patients with benign breast disease,
and 20 normal healthy volunteers were detected with nested reverse transcription-polymerase chain reaction (Nested-RT-PCR).
ResultsSBEM-mRNA was negative in healthy individuals and patients with benign breast tumor, but 50.7%(34/67) of breast cancer patients
showed positive expression of SBEM-mRNA in peripheral blood, of whom 25%(2/8) were in stage I, 45.8%(11/24) in stage II, 43.75%(11/24)
in stage III and 73.7(14/19) in stage IV. The positive rate in stage IV was higher than that in stage I, II, III (P<0.05). Expressions of SBEM-mRNA had no correlation with age, carcinoma size, pathological type, ER and PR state (P<0.05).
ConclusionSEBM-mRNA is specifically expressed in breast cancer and it may act as a marker for the detection of micrometastasis of breast
Chinese Journal of Cancer Research 01/2006; 18(4):294-298. DOI:10.1007/s11670-006-0294-4 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The major cause of death in breast cancer patients is distant metastasis. This study was to explore the expression and significance of small breast epithelial mucin (SBEM) mRNA, the specific marker of breast cancer, in peripheral blood of breast cancer patients.
Expression of SBEM mRNA in peripheral blood samples from 67 breast cancer patients, 16 benign breast disease patients, and 20 healthy volunteers was detected by nested reverse transcription-polymerase chain reaction (nested RT-PCR).
SBEM mRNA was not detected in healthy volunteers and benign breast disease patients. Positive rate of SBEM mRNA was 50.7% (34/67) in breast cancer patients. Positive rate of SBEM mRNA was 25.0% (2/8) in stage I patients, 45.8% (11/24) in stage II patients, 43.8% (7/16) in stage III patients, and 73.7% (14/19) in stage IV patients, respectively. Positive rate of SBEM mRNA was significantly higher in stage IV patients than in stages I, II, and III patients (P0.05). The expression of SBEM mRNA in peripheral blood was not correlated with patient's age, primary tumor size, pathologic type, and estrogen or progestin receptor status (P0.05).
SBEM mRNA is specifically expressed in peripheral blood of breast cancer patients, and may be a marker of micrometastasis of breast cancer.
Ai zheng = Aizheng = Chinese journal of cancer 08/2005; 24(7):842-5. · 2.16 Impact Factor