Biochemical changes during regression and regrowth of hormone-dependent GR mouse mammary tumors.

Abstract

Discontinuation of recommencement of estrone-progesterone treatment causes regression and regrowth, respectively, of transplantable hormone-dependent GR mouse mammary tumors. This tumor model was found convenient for the demonstration of hormonal responses in hormone-dependent mouse mammary tumor cells. Tumor regression was palpable 2 days after discontinuation of hormonal treatment and tumors reached half their size within 3-6 days. At this point, hormones were readministered and 2-4 days later the tumors had grown to their preregression size. In the growing and regressing tumor we have investigated: (1) the content of RNA, DNA and protein per g wet weight, (2) in vivo incorporation for 45 min of 32P-orthophosphate into RNA and DNA and the 35S-methionine incorporation into protine; (3) SDS polyacrylamide gel electrophoresis of soluble proteins after in vivo incorporation of 14C- and 3H-leucine. The RNA content per g wet weight was found to decrease during regression and to increase during regrowth. DNA and protein content showed no variation. RNA/DNA ratio thus varied in parallel to the RNA content. The precuursor incorporation into all three macromolecular species decreased during regression. The incorporation into DNA showed the most pronounced decrease. After readministration of hormones, regrowth was accompanied by a rapid increase in precursor incorporation into RNA, while the incorporation into DNA showed a lag of 1 to 2 days. SDS polyacrylamide gel electrophoresis was carried out with soluble proteins labelled in vivo with 14C- and 3H-leucine during regression and regrowth, respectively. No differences in 14C/3H ratios could be demonstrated for the major fractions detectable in the electropherogram.