Association of in vitro invasiveness and gene expression of estrogen receptor, progesterone receptor, pS2 and plasminogen activator inhibitor-1 in human breast cancer cell lines.
ABSTRACT 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.
Full-textDOI: · Available from: Dan Cacsire Castillo-Tong, May 29, 2015
SourceAvailable from: Hazem Ghebeh[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 · 4.82 Impact Factor
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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.Diagnostic Pathology 07/2014; 9(1):136. DOI:10.1186/1746-1596-9-136 · 2.41 Impact Factor
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ABSTRACT: Identification of protein targets, which play a role in breast cancer invasion may help in understanding the rapid progression of cancer and may lead to the development of new biomarkers for the disease. In this study, we have compared two highly invasive and two poorly invasive breast cancer cell lines using comparative label-free LC-MS profiling in order to identify differentially expressed proteins that may be linked to the invasive phenotype in vitro. Forty-five proteins were found to be up-regulated and 34 proteins to be down-regulated respectively. UV excision repair protein RAD23 homologue B (RAD23B) was found amongst the down-regulated proteins in highly invasive breast cancer cell lines. In poorly invasive breast cancer cell lines, siRNA mediated down-regulation of RAD23B subsequently led to an increase in invasion and adhesion in vitro. Immunohistochemistry analysis of 164 specimens of invasive breast cancer showed that a high percentage (>80%) of RAD23B positive nuclei was significantly associated with histopathological grade 1 and 2 breast cancers and with low mitotic activity. In addition, a high staining intensity for RAD23B in the cytoplasm was significantly associated with histopathological grade 3 breast cancers. This study suggests a potential role of RAD23B in breast cancer progression and may further imply a tumour suppressor role of nuclear RAD23B in breast cancer.Journal of Proteome Research 06/2014; 13(7). DOI:10.1021/pr4012156 · 5.00 Impact Factor