Induction of apoptosis in melanoma cell lines by p53 and its related proteins

Melanoma cells rarely contain mutant p53 and hardly undergo apoptosis by wi ld-type p53. By using recombinant adenoviruses that express p53 or p53-rela ted p51A or p73 beta, we tested their apoptotic activities in melanoma cell s. Yeast functional assay revealed a mutation of p53 at the 258th codon (AA A [K] instead of GAA [E]) in one cell line, 70W, out of six human melanoma cell fines analyzed (SK-mel-23, SK-mel-24, SK-mel-118, TXM18, 70W, and G361 ). Adenovirus-mediated transfer of p53, p51A, and/or p73 beta suppressed gr owth and induced apoptotic DNA fragmentation of SK-mel-23, SK-mel-118, and 70W cells. Interestingly, p51A induced DNA fragmentation in them more signi ficantly than p53 and p73 beta. Western blotting we analyzed levels of apop tosis-related proteins in cells expressing p53 family members. Apoptotic Ba x and antiapoptotic Bcl-2 were not significantly upregulated or downregulat ed by expression of p53, p51A, or p73 beta, except for p53-expressing 70W c ells, which contained a larger amount of Bax protein than LacZ-expressing c ells. Activation of caspase-3 was demonstrated only in p51A-expressing SK-m el-118 cells. We show here that p51A can mediate apoptosis in both wild-typ e and mutant p53-expressing melanoma cells more significantly than p53 and p73 beta. It is also suggested that in melanoma cells (i) cellular target p rotein(s) other than Bcl-2 and Bax might be responsible for induction of p5 1A-mediated apoptosis and (ii) caspase-3 is not always involved in the apop tosis by p53 family members.