title: Up-regulation of ras-GAP genes is reversed by a MEK inhibitor and doxorubicin in v-Ki-ras-transformed NIH/3T3 fibroblasts.
abstract: Ras-GTPase-activating proteins (Ras-GAPs) have been implicated both as suppressors of Ras and as effectors in regulating cellular activities. To study whether Ras-GAPs have roles in tumor cell survival or not, mRNA levels of ras-related genes were measured in v-Ki-ras-transformed (DT) and the parental NIH/3T3 cells, using real-time PCR. mRNA levels of p120-Gap, Gap1(m), and PIK3CA were increased in DT cells compared with NIH/3T3 cells. p120-Gap and PIK3CA genes were induced by addition of serum or epidermal growth factor to serum-starved DT cells. Three anti-cancer drugs, an ERK kinase (MEK) inhibitor PD98059, a topoisomerase II poison doxorubicin (adriamycin), and a histone deacetylase inhibitor trichostatin A, selectively blocked the overexpression of p120-Gap and Gap1(m) genes in DT cells. These drugs also caused reversion of DT cells to the adherent shape associated with growth arrest. Our results suggest that p120-Gap and Gap1(m) genes provide important biomarkers for cancer therapies.
authors: Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. mhashii@med.kanazawa-u.ac.jp
authors: Minako
authors: M
authors: Hashii
authors: Mitsunori
authors: M
authors: Fukuda
authors: Hideki
authors: H
authors: Nomura
authors: Naoko
authors: N
authors: Ito
authors: Hiroto
authors: H
authors: Takahashi
authors: Seisuke
authors: S
authors: Hattori
authors: Katsuhiko
authors: K
authors: Mikoshiba
authors: Makoto
authors: M
authors: Noda
authors: Yoshihiro
authors: Y
authors: Higuchi
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002461:Cell Line, Transformed; D004317:Doxorubicin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D011905:Genes, ras / Q000502:physiology*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020703:ras GTPase-Activating Proteins; D004317:Doxorubicin; D020929:Mitogen-Activated Protein Kinase Kinases