Downregulation of proapoptotic proteins Bax and Bcl-X-s in p53 overexpressing hepatocellular carcinomas

As the occurrence of structural p53 mutations in hepatocellular carcinoma ( HCC) in Thailand was previously reported to be much lower than that found i n other high-incidence HCC areas, we analyzed 16 HCC samples from Thailand to determine the expression and functionality of p53 protein. We observed t he overexpression of p53 protein in 69% of HCC, despite the prevalence of t he wild-type p53 gene. However, the overexpressed p53 protein was nonfuncti onal as suggested by its inability to modulate the expressions of several p 53 effector proteins (p21 and Bcl-2 family proteins). In addition, we obser ved significant underexpression of two proapoptotic proteins, Bax and Bcl-X -s, in 81% (P = 0.02) and 64% (P = 0.03) of HCC, respectively. Consequently , the ratios of proapoptotic to antiapoptotic BCL-2 family proteins were re duced in 88% of the HCC tumor tissues when compared to normal tissues, such that the rheostat between BCL-2 family proteins is strongly skewed toward enhanced cell survival in the tumor cells. (C) 2000 Academic Press.