Concurrent changes in growth-related biochemical parameters during regression of hormone-dependent rat mammary tumors.

The in vivo relationship was studied between these biochemical parameters which previous studies have separately implicated in the regression of hormone-dependent rat mammary tumors. Upon depletion of estrogen and suppression of prolactin levels by ovariectomy, there was a marked increase in the production of prostaglandin E2 (PGE2)(fourfold) and in the cyclic AMP (cAMP) content (twofold) in the regressing 7,12-dimethylbenz[a]anthracene-induced primary tumors. These two parameters appeared to be coupled since, in addition to this correlation, PGE2 stimulated adenylate cyclase and raised cAMP levels in both this primary tumor system and in another hormone-dependent transplantable rat mammary tumor (MTW9-A). Furthermore both the sensitivity of the adenylate cyclase system to PGE2 and the number of membrane binding sites for PGE2 increased upon induction of regression in these tumors. Under conditions where PGE2 and cAMP were elevated, (i.e., in regressing, but not growing, hormone-dependent mammary tumors), there was significant phosphorylation in the intact tissue of a 75,000-dalton nuclear protein, which appeared to be identical to the regression-associated protein shown by Cho-Chung and co-workers to undergo increased phosphorylation in response to elevated cAMP levels.