title: Microarray determination of Bcl-2 family protein inhibition sensitivity in breast cancer cells.
abstract: This study tests the hypothesis that reverse transcription polymerase chain reaction (RT-PCR) microarrays can be used to predict the relative sensitivity to induction of apoptosis in breast cancer cells exposed to inhibitors of antiapoptotic Bcl-2 family proteins. Four cell lines, MDA-MB-231 (MDA-231) and MDA-MB-468 (MDA-468), BT-20 and T47-D were screened for relative expression of Bcl-2 family members A1, Mcl-1, Bcl-2, Bcl-xL and Bcl-w mRNA by RT-PCR microarrays and Western analysis. The four cell lines were treated with 1 μmol/L obatoclax (GX15-070) and/or 2 Gy radiation (RT) and monitored for apoptosis after 48 h. Cell lines showing the highest total fold-increase of Bcl-2 family member mRNA, MDA-231 and MDA-468, also showed the highest levels of apoptosis induction (approximately 70% with obatoclax alone and 82% with obatoclax plus RT). Cell lines with little or no increase in Bcl-2 family mRNA (BT-20 and T47-D) showed less apoptosis (30% following treatment with obatoclax and 42% with obatoclax plus RT). RT-PCR arrays can predict the relative apoptosis response of breast cancer cells to the pan Bcl-2 inhibitor obatoclax alone or when combined with radiation.
authors.affiliation: Department of Radiation Oncology, The State University of New York Upstate Medical University, Syracuse, NY 13210, USA. hudsons@upstate.edu
authors.forename: Sandra G
authors.initials: SG
authors.lastname: Hudson
authors.forename: Devin R
authors.initials: DR
authors.lastname: Halleran
authors.forename: Barbara
authors.initials: B
authors.lastname: Nevaldine
authors.forename: Anna
authors.initials: A
authors.lastname: Shapiro
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hutchison
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hahn
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005720:Gamma Rays; D006801:Humans; D007211:Indoles; D046228:Microarray Analysis / Q000379:methods*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; C520962:obatoclax