Effect of procathepsin D activation peptide on gene expression of breast cancer cells.
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.
Benes
Petr
P
Department of Genetics and Molecular Biology, Faculty of Science, Masaryk University Brno, Kotlarska 2, Brno 61137, Czech Republic. pbenes@sci.muni.cz
Vashishta
Aruna
A
Saraswat-Ohri
Sujata
S
Fusek
Martin
M
Pospisilova
Sarka
S
Tichy
Boris
B
Vetvicka
Vaclav
V
D001943:Breast Neoplasms / Q000235:genetics*; D002402:Cathepsin D / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D052003:NF-kappa B p52 Subunit / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D004792:Enzyme Precursors; D052003:NF-kappa B p52 Subunit; D009363:Neoplasm Proteins; D010446:Peptide Fragments; C058345:procathepsin D; D002402:Cathepsin D