Effect of procathepsin D activation peptide on gene expression of breast cancer cells
Petr Benes1, Aruna Vashishta, Sujata Saraswat-Ohri
1Department of Genetics and Molecular Biology, Faculty of Science, Masaryk University Brno, Kotlarska 2, Brno 61137, Czech Republic. pbenes@sci.muni.cz
Abstract:
Overexpression of procathepsin D (pCD) is reported to occur in numerous types of cancer and is associated with increased growth and metastasis. It has been established that pCD affects multiple stages of tumor progression including proliferation, angiogenesis and metastasis. Previously, we showed that the mitogenic effect of pCD on cancer cells is mediated by interaction of its activation peptide (AP) with yet unidentified cell surface receptor. In this investigation, gene expression profiles were compared between AP-treated and control human breast cancer ZR-75-1 cells to elucidate the mechanism of AP mitogenicity. Several differentially expressed genes involved in signal transduction, regulation of cell cycle, apoptosis, tumor invasion and metastasis were identified using microarray technology. These findings, including overexpression of NF-kappaB2, were confirmed in breast cancer cell lines by reverse-transcriptase PCR (RT-PCR). Understanding the mechanism of pCDs effect on breast cancer cells could extend possibilities of breast cancer treatment in the future.
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