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: Sandra G Hudson, Devin R Halleran, Barbara Nevaldine, Anna Shapiro, Robert E Hutchison, Peter J Hahn
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 238 Issue 2 Pg. 248-56 (Feb 2013) ISSN: 1535-3699 [Electronic] England
• PMID: 23576806 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Indoles
• Proto-Oncogene Proteins c-bcl-2
• Pyrroles
• obatoclax

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Blotting, Western
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Drug Screening Assays, Antitumor (methods)
• Gamma Rays
• Humans
• Indoles
• Microarray Analysis (methods)
• Proto-Oncogene Proteins c-bcl-2 (antagonists & inhibitors)
• Pyrroles (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction (methods)