PMID- 11691828 OWN - NLM STAT- MEDLINE DCOM- 20011204 LR - 20161124 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 61 IP - 21 DP - 2001 Nov 1 TI - Altered gene expression pattern in cultured human breast cancer cells treated with hepatocyte growth factor/scatter factor in the setting of DNA damage. PG - 8022-31 AB - 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. FAU - Yuan, R AU - Yuan R AD - Department of Radiation Oncology, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA. FAU - Fan, S AU - Fan S FAU - Achary, M AU - Achary M FAU - Stewart, D M AU - Stewart DM FAU - Goldberg, I D AU - Goldberg ID FAU - Rosen, E M AU - Rosen EM LA - eng GR - R01-80000/PHS HHS/United States GR - R01-82599/PHS HHS/United States GR - R01-ES09169/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Minor Histocompatibility Antigens) RN - 0 (RNA, Messenger) RN - 0 (TRIP10 protein, human) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 80168379AG (Doxorubicin) SB - IM MH - Antibiotics, Antineoplastic/pharmacology MH - Breast Neoplasms/*genetics/metabolism MH - DNA Damage/*physiology MH - Doxorubicin/pharmacology MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Hepatocyte Growth Factor/*pharmacology MH - Humans MH - Microtubule-Associated Proteins/physiology MH - Minor Histocompatibility Antigens MH - Oligonucleotide Array Sequence Analysis MH - RNA, Messenger/biosynthesis/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Cells, Cultured/drug effects EDAT- 2001/11/03 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/11/03 10:00 PHST- 2001/11/03 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/11/03 10:00 [entrez] PST - ppublish SO - Cancer Res. 2001 Nov 1;61(21):8022-31.