Journal
JOURNAL OF PATHOLOGY
Volume 199, Issue 3, Pages 275-288Publisher
WILEY
DOI: 10.1002/path.1300
Keywords
pro-apoptotic molecules; anti-apoptotic molecules; CMM; cutaneous malignant melanoma; programmed cell death
Funding
- NIAMS NIH HHS [AR02136] Funding Source: Medline
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Melanoma cells can undergo self-destruction via programmed cell death, i.e. apoptosis. In these tumours, the molecular components of apoptosis include positive (apoptotic) and negative (anti-apoptotic) regulators. The former include p53, Bid, Noxa, PUMA, Bax, TNF, TRAIL, Fas/FasL, PITSLRE, interferons, and c-KIT/SCF. The latter include Bcl-2, Bcl-X-L, Mcl-1, NF-B-K, survivin, livin, and ML-IAP. Alternatively, some molecules such as TRAF-2, c-Myc, endothelins, and integrins may have either pro- or anti-apoptotic effects. Some of these molecules are of potential therapeutic use, such as: (1) p53, which influences resistance to chemotherapy; (2) Mcl-1 and Bcl-X-L, which can override apoptosis; (3) TRAIL, which has selective fatal effects on tumour cells; (4) NF-B-K, which when downregulated sensitizes cells to TRAIL and TNF; (5) the PITSLRE kinases, whose alteration appears to result in Fas resistance; (6) interferons, which sensitize cells to other factors; and (7) survivin and other IAPs that inhibit apoptosis. This review summarizes the state of current knowledge about the key molecular components and mechanisms of apoptosis in melanoma, discusses potential therapeutic ramifications, and provides directions for future research. Copyright (C) 2003 John Wiley Sons, Ltd.
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