期刊
MELANOMA RESEARCH
卷 22, 期 3, 页码 244-251出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CMR.0b013e328353eff2
关键词
apoptosis; Bim; BRAF inhibitors; in vivo; melanoma; splicing
资金
- NSW State Cancer Council
- National Health and Medical Research Council (NHMRC), Australia
- NHMRC
Relatively little attention has been paid to the activity of selective BRAF inhibitors in the induction of apoptosis in melanoma, particularly in vivo. In the present study, we have isolated cultures from biopsies taken from four patients before and during the treatment of their melanoma. We report that the cell lines taken during treatment show varying degrees of upregulation of the proapoptotic BH3 protein Bim and its splice forms, downregulation of Mcl-1, and upregulation of the splicing factor SRp55 as reported in previous in-vitro studies. There was also evidence of ongoing apoptotic signaling despite the continued growth of the cultures. The cultures established during the treatment were largely resistant to the selective BRAF inhibitor PLX4720, consistent with the acquired resistance of melanoma in the treated patients. These results provide further insights into the mechanism of action of these agents against melanoma. Melanoma Res 22: 244-251 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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