CELL-SURVIVAL EFFECT OF ACTIVIN AGAINST HEAT-SHOCK STRESS ON OVCAR3

Activin has been known as the hormone protein which regulates either c ell proliferation or cell differentiation. Recently, it has also been reported that activin may have cell survival function. In this study, we have investigated, 1) the expression of inhibin subunits and activi n receptors ( ActRs) in ovarian carcinoma cell line ( OVCAR3) 2) the b inding property between activin and its receptors under the exposure t o stress,and 3) the effect of activin on cell proliferation. All of in hibin subunits and ActR la, IIa and IIb mRNA were amplified by RT-PCR in OVCAR3. By Western blot analysis,ActR IIa and IIb proteins were det ected. The binding property between activin and ActRs was analyzed wit h the fixed complex, using chemical cross linker. The bigger molecular weight signals, which had been shown to form the heterotrimeric compl ex among activin, ActR type I and ActR type II were detected after cro ss linking. These upper signals were apparently increased by rh-Activi n and decreased by rh-follistatin. Therefore, it was suggested that th ey were resultant from activin and Act-R complex. OVCAR3 was exposed t o the stress ( 42C, 1 hour heat shock), the protein level of ActR IIa increased and ActR IIb decreased from about 3h to 24h after the exposu re to the heat stress (HS). On the other hand, the complex between act ivin and ActR IIa and IIb increased from 3h after the exposure to HS. To investigate the effect of activin and follistatin on OVCAR3 prolife ration after the exposure to HS, we counted the cell number at 96 h af ter the treatment with activin or follistatin in the condition either with or without HS. Proliferation of the cell in the presence of HS wa s stimulated by rh-Activin and inhibited by rh-follistatin. These data suggest that activin might have the function to survive and to prolif erate OVCAR3, due to, at least in part the increase in its binding cap acity to ActRs through either autocrine or paracrine manner.