THE GROWTH SUPPRESSOR PROTEIN P53, ITS CE LLULAR PARTNERS AND CARCINOMA OF THE PROSTATE

The growth suppressor protein p53 is mutated in more than 50% of all h uman tumours. In prostate carcinoma genetic alterations and an elevate d p53 protein expression seems to be restricted to late stages of inva sive prostate carcinoma. Wild-type p53 regulates the expression of var ious cellular genes and it binds to an increasing number of cellular p roteins. Binding to these proteins must be considered as playing a reg ulatory role in early stages of prostate carcinoma. Genetic alteration s in the p21(WAF1) gene and an altered expression, subcellular localiz ation and enzymatic activity of protein kinase CK2 have been described for prostate carcinoma. The p21(WAF1) gene is a downstream element of the p53 regulatory pathway. CK2 is a cellular p53 binding protein and by this interaction the enzymatic activity of CK2 as well as the DNA binding activity of p53 are regulated. p53 is usually detected in the nucleus by immunohistochemistry. However, in prostate carcinoma cells at least an immunologically defined subclass of p53 is found in the nu cleoli. An initial gene therapeutic approach in an animal model reveal ed that wild-type p53 and p21(WAF1) inhibit the growth of prostate car cinoma cells. Hence, these results demonstrate that not only p53 but a lso its cellular partner molecules must be considered for the diagnosi s, prognosis and therapy of prostate carcinoma.