HORMONAL-CONTROL OF GROWTH AND PROGRESSION IN TUMORS OF NB RATS AND A THEORY OF ACTION

Abstract

A continuation of previous studies of hormone-dependent tumors in various organs in Nb rats concerns the effects of removal of the hormone stimulus from animals with growing tumors. Tumor regression usually followed this procedure, and in various models it was associated with increased survival of the animal. A regressed tumor could be caused to grow at any time by estrogen treatment, and the resulting tumor remained hormone dependent, although some progression might occur. Continuous breeding rarely affected growth or progression of transplanted adrenal or breast carcinomas. When spontaneous regrowth of tumors took place following removal of the estrogen stimulus, all types of tumors (except leiomyomas of the uterus) showed progression usually to autonomy, and in the case of male rats bearing breast carcinomas it was inevitable. The substitution of pellets containing a reduced level of estrone, to determine which prevented regression and allowed uninterrupted growth, offered an assessment of the type or amount of hormone required for the growth of different tumors. By means of such a model of breast cancer in male rats, it was possible to demonstrate that a reduction in hormone levels sufficient to prevent advancing tumor growth, but adequate to reduce the extent of regression, also reduced the frequency or prevented the development of autonomous change. Although regression per se was not a prerequisite for autonomous change, the paradox was evident that progression towards autonomous growth was accelerated with procedures expected to check tumor growth and was minimal with procedures that accelerated it. Liver metastases of hormone-dependent adrenal carcinomas continued growth and could not be influenced by removal of estrogen, although the primary transplant regressed. When such metastases were transplanted, they did not progress to autonomy but retained a hormone-dependent status. Some tumors, when maintained in estrogen-conditioned hosts, showed a reversion to a more hormone-dependent cell type rather than the expected progression toward autonomy. A theory is suggested to explain the experimental findings on the development and control of estrogen responsive tumors.