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 an 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 the 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 were not found to have progressed to autonomy but retained a hormone-dependent status. Some tumors, when maintained in estrogen-conditioned hosts, apparently showed a reversion to a more hormone-dependent cell type rather than the expected progression towards autonomy. A theory is suggested to explain the experiments findings on the development and control of estrogen-responsive tumors.

PIP: The effect of the removal of estrogen stimulus on the growth and progression of hormone-dependent tumors in various organs in Nb strain rats was investigated. Withdrawal of estrogen usually brought about regression of the tumor and, in some cases, an increased survival period. However, resumption of treatment caused a hormone-dependent growth of any regressed tumor, though progression was observed in some cases. In cases of spontaneous regrowth, all types of tumors, excepting leiomyomas of the uterus, showed progression and usually became autonomous. In experiments with pellets containing a reduced level of estrone, it was possible to prevent advancing tumor growth yet reduce the extent of regression, and at the same time reduce the frequency or prevent the development of autonomous change. Paradoxically, progression toward autonomous growth was stimulated by regimes expected to halt tumor growth and minimized by procedures that were expected to stimulate it. Transplanted liver metastases of hormone-dependent adrenal carcinomas retained their hormone dependence, even though the donor metastases continued growth despite removal of estrogen influence. A theory is offered to explain the results.