Control of cell cycle regulatory proteins and modulation of STAT1 proteins by IFN-_γ in human prostatic JCA-1 cells

The addition of human recombinant IFN-_γ (10² and 10³ IU/ml) inhibited human prostatic JCA-1 cell growth by 27% and '64%, respectively. Since the high dose of IFN-_γ elicited an increase in G₁ concomitant with a decrease in G₂/M phases of the cell cycle, changes in the expression of cell cycle regulatory protein molecules were analyzed by Western blots. Results of these experiments show that IFN-_γ down regulated the G₁/S transition molecules, e.g., cyclin D1, the cyclin-dependent protein kinase Cdk4, and the retinoblastoma gene product (pRB), but increased the G₂/M transition molecules, e.g., cyclin B1 and p34^cdc2 (Cdk1). Possible modulation of Cdk-inhibitors (CDKIs), e.g., p53 and p21^WAF1 which have checkpoint functions in the cell cycle, by IFN-_γ, was also studied. The p53 was induced by both 10² and 10³ IU/ml IFN-_γ. At 10³ IU/ml, IFN-_γ inhibited p21^WAF1, increased the expression of STATlα, and sustained the elevated STAT1α for up to 96 h. Thus several mechanisms may be involved in the antiproliferative effects of IFN-_γ.