Tong D, Czerwenka K, Sedlak J, Schneeberger C, Schiebel I, Concin N, Leodolter S, Zeillinger RAssociation of in vitro invasiveness and gene expression of estrogen receptor, progesterone receptor, pS2 and plasminogen activator inhibitor-1 in human breast cancer cell lines. Breast Cancer Res Treat 56(1): 91-97

Division of Gynecology, Molecular Oncology Group, University of Vienna, Austria.
Breast Cancer Research and Treatment (Impact Factor: 3.94). 08/1999; 56(1):91-7. DOI: 10.1023/A:1006262501062
Source: PubMed


The invasive potential of tumor cells is usually tested either by in vitro invasion assays which evaluate cell spreading ability in basement membrane-like matrices or by in vivo invasion assays in nude mice. Both methods are laborious and time-consuming. Tumor invasiveness is accompanied by the changes in expression of various genes. The invasive behavior of cells is therefore represented by certain gene expression patterns. The purpose of this study was to investigate whether expression patterns of several genes are characteristic for the invasiveness of cultured cells. We examined the mRNA levels of estrogen receptor (ER), progesterone receptor (PR), estrogen inducible pS2 and plasminogen activator inhibitor-1 (PAI-1) in 23 cell lines derived from benign and malignant breast tissues using a competitive reverse transcription-polymerase chain reaction (cRT-PCR) system. We also evaluated the invasiveness of these cell lines by their ability to penetrate into a collagen-fibroblast matrix. We demonstrate that the gene expression pattern of breast cell lines is clearly associated with their in vitro invasiveness. In general, cells with ER, PR, pS2 but no PAI-1 expression showed a non-invasive phenotype, while cells expressing PAI-1 mRNA but not ER mRNA are invasive. Our study indicates that the invasiveness of breast cancer cell lines is characterized by PAI-1 gene expression and the lack of ER mRNA. This suggests that PAI-1 may participate in the invasive process.

Download full-text


Available from: Dan Cacsire Castillo-Tong,
  • Source
    • "Fascin-positive xenograft tumour is more resistant to the chemotherapeutic agent doxorubicin. To evaluate if fascin expression in breast cancer cells can directly contribute to their chemotherapy resistance, we used the tumorigenic and fascinpositive MDA-MB-231 breast cancer cells in a xenograft tumour model (Rochefort et al, 1998; Tong et al, 1999 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: A major therapeutic challenge for breast cancer is the ability of cancer cells to evade killing of conventional chemotherapeutic agents. We have recently reported the actin-bundling protein (fascin) as a major regulator of breast cancer metastasis and survival. Methods: Survival of breast cancer patients that received chemotherapy and xenograft tumour model was used to assess the effect of chemotherapy on fascin-positive and -negative breast cancer cells. Molecular and cellular assays were used to gain in-depth understanding of the relationship between fascin and chemoresistance. Results: We showed a significant correlation between fascin expression and shorter survival in breast cancer patients who received chemotherapy. In xenograft experiments, fascin-positive cancer cells displayed significantly more resistance to chemotherapy-mediated apoptotic cell death than fascin-negative counterparts. This increased chemoresistance was at least partially mediated through PI3K/Akt signalling, and was paralleled by increased FAK phosphorylation, enhanced expression of the inhibitor of apoptosis proteins (XIAP and Livin) and suppression of the proapoptotic markers (caspase 9, caspase 3 and PARP). Conclusions: This is the first report to demonstrate fascin involvement in breast cancer chemotherapeutic resistance, supporting the development of fascin-targeting drugs for better treatment of chemoresistance breast cancer.
    British Journal of Cancer 08/2014; 111(8). DOI:10.1038/bjc.2014.453 · 4.84 Impact Factor
  • Source
    • "Hormone receptor–negative breast cancers traditionally have a worse prognosis and fewer available treatment options (ineffectiveness of hormonal therapy) compared with hormone receptor–positive tumors [34-36]. It is interesting that hormone receptor–negative breast cancers also display increased cell motility in vitro [37,38]. In a study examining the ability of breast cancer cell lines to penetrate into a collagen-fibroblast matrix, cells expressing mRNA for estrogen receptor showed a noninvasive phenotype, whereas cells lacking estrogen receptor mRNA were shown to be highly invasive [38]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of fascin on cell invasiveness involve changes in cell motility and matrix metalloproteinase-9 (MMP-9) activity. Previous studies on the prognostic value of fascin and MMP-9 in breast carcinoma revealed conflicting results. To date, no immunohistochemical studies have been performed to assess the possible association between them in breast carcinoma. This study is designed to correlate their expression with prognostic parameters in breast carcinoma and assess the relationship between them. Immunohistochemical expression of fascin and MMP-9 was evaluated semi quantitatively in 67 cases of breast carcinoma regarding the percentage of positive cells. Chi square test and Fisher’s exact test were used to examine the relationship between categorical variables. Kappa statistics was used to compute the measure of agreement between two investigational methods. Fascin and MMP-9 expressions were detected in 43.28% and 50.75% of breast carcinomas (respectively). Regarding the normal breast tissue, fascin expression was observed in myoepithelial cells and luminal cells of few ducts and acini. However, normal tissue showed negative MMP-9 expression. A significant relationship was observed between fascin and MMP-9 expression and lymph node metastases (p = 0.001 and 0.002 respectively), advanced tumor stage (p = 0.004 and 0.005 respectively), estrogen receptor negative (p = 0.002 and 0.005 respectively), progesterone receptor negative (p = 0.001 and 0.003 respectively) hormonal status and molecular subtypes (p = 0.0007 and 0.014 respectively). A significant strong agreement was detected between fascin and MMP-9 expression (p = 0.0001). More intense immunostaining of fascin and MMP-9 was observed at the invasive fronts compared with other areas of the tumor. Moreover, a significant moderate agreement between fascin and MMP-9 was found regarding the site of predominant intensity. Fascin and MMP-9 proteins are associated with parameters of poor prognosis in breast cancer. The significant strong agreement between the two markers supports the role of fascin in cell invasiveness by activating matrix proteases besides increasing cell motility. Both proteins may represent potential therapeutic targets for patients with breast cancer especially those with hormone receptor–negative status. Virtual slides The virtual slide(s) for this article can be found here:
    Diagnostic Pathology 07/2014; 9(1):136. DOI:10.1186/1746-1596-9-136 · 2.60 Impact Factor
  • Source
    • "Thermal cycling and fluorescence detection were conducted on a Thermal Cycler Dice® Real Time System (Takara), in accordance with the manufacturer's instructions, at 94°C for 2 min, followed by 40 cycles of 94°C for 20 sec, 55°C for 20 sec and 72°C for 40 sec. Each reaction was performed in triplicate (17). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Taspine is an attractive target of research due to the anticancer and anti-angiogenic effects shown by in vitro and in vivo experiments. The present study investigated the role of tas1611, which is a derivative of taspine that has increased activity and solubility, in the regulation of the invasive properties of the SMMC-7721 liver cell line in vitro and in tumor inhibition in vivo. The proliferation of the SMMC-7721 cells was examined using the tetrazole blue colorimetric method. Matrigel(®) invasion chamber assays and zymogram analyses were performed to assess the inhibitory effect of tas1611 on cell invasion. Finally, a solid tumor athymic mouse model was employed to further investigate the anti-tumor effect of this compound. The results revealed that tas1611 had a marked inhibitory effect on the invasion of the SMMC-7721 cells and that this effect was associated with the activity and expression levels of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, tas1611 was able to inhibit tumor growth effectively in a solid tumor SMMC-7721 athymic mouse model. In conclusion, tas1611 may serve as a promising novel therapeutic candidate for the treatment of metastatic liver cancer.
    Oncology letters 09/2013; 6(3):855-859. DOI:10.3892/ol.2013.1452 · 1.55 Impact Factor
Show more