Altered gene expression pattern in cultured human breast cancer cells treated with hepatocyte growth factor/scatter factor in the setting of DNA damage
| Autor: | R, Yuan, S, Fan, M, Achary, D M, Stewart, I D, Goldberg, E M, Rosen |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Antibiotics
Antineoplastic Hepatocyte Growth Factor Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Breast Neoplasms Gene Expression Regulation Neoplastic Minor Histocompatibility Antigens Doxorubicin Tumor Cells Cultured Humans RNA Messenger Microtubule-Associated Proteins DNA Damage Oligonucleotide Array Sequence Analysis |
| Zdroj: | Cancer research. 61(21) |
| ISSN: | 0008-5472 |
| Popis: | The cytokine hepatocyte growth factor/scatter factor (HGF/SF) protects epithelial and cancer cells against DNA-damaging agents via a pathway involving signaling from c-Met --phosphatidylinositol-3- kinase --c-Akt. However, the downstream alterations in gene expression resulting from this pathway have not been established. On the basis of cDNA microarray and semiquantitative RT-PCR assays, we found that MDA-MB-453 human breast cancer cells preincubated with HGF/SF and then exposed to Adriamycin (ADR), a DNA topoisomerase II inhibitor, exhibit an altered pattern of gene expression, as compared with cells treated with ADR only. [HGF/SF+ADR]-treated cells showed altered expression of genes involved in the DNA damage response, cell cycle regulation, signal transduction, metabolism, and development. Some of these alterations suggest mechanisms by which HGF/SF may exert its protective activity, e.g., up-regulation of polycystic kidney disease-1 (a survival-promoting component of cadherin-catenin complexes), down-regulation of 51C (an inositol polyphosphate-5-phosphatase), and down-regulation of TOPBP1 (a topoisomerase IIB binding protein). We showed that enforced expression of the cdc42-interacting protein CIP4, a cytoskeleton-associated protein for which expression was decreased in [HGF/SF+ADR]-treated cells, inhibited HGF/SF-mediated protection against ADR. The cDNA microarray approach may open up new avenues for investigation of the DNA damage response and its regulation by HGF/SF. |
| Databáze: | OpenAIRE |
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