Effect of procathepsin D activation peptide on gene expression of breast cancer cells.

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.

• Authors: Petr Benes, Aruna Vashishta, Sujata Saraswat-Ohri, Martin Fusek, Sarka Pospisilova, Boris Tichy, Vaclav Vetvicka
• Journal: Cancer letters (Cancer Lett) Vol. 239 Issue 1 Pg. 46-54 (Jul 28 2006) ISSN: 0304-3835 [Print] Ireland
• PMID: 16168559 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Precursors
• NF-kappa B p52 Subunit
• Neoplasm Proteins
• Peptide Fragments
• procathepsin D
• Cathepsin D

Topics

• Breast Neoplasms (genetics)
• Cathepsin D (pharmacology)
• Enzyme Precursors (pharmacology)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• NF-kappa B p52 Subunit (genetics, metabolism)
• Neoplasm Proteins (genetics)
• Oligonucleotide Array Sequence Analysis
• Peptide Fragments (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Tumor Cells, Cultured