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Increased Susceptibility of Cytosol Proteins to Proteolytic Digestion during Regression of a Hormone-dependent Mammary Tumor¹

Laboratory of Pathophysiology, National Cancer Institute, NIH, Bethesda, Maryland 20014

Regression of MTW9 mammary carcinoma, which consistently follows withdrawal of mammotropic hormones, was characterized by a rapid decrease of thymidine incorporation into DNA but only a slight reduction of uridine incorporation into RNA and amino acid incorporation into proteins. Within 24 hr of hormone withdrawal, cytosol proteins of MTW9 became more easily degraded by trypsin, -chymotrypsin, or subtilisin BPN'. Labilization of cytosol proteins occurred much earlier than any change in the level of protein synthesis or lysosomal enzyme activity. The data showing increased susceptibility to proteolysis could not be explained either by the presence of endogenous proteases, by the destruction of the exogenous proteases used in the assay, or by the existence of protease inhibitors. Nor were any differences detected either in the distribution of radioactive precursor among the cytosol proteins from growing or regressing tumors or in the electrophoretic pattern of the same proteins. Preincubation of the cytosol proteins with dithiothreitol or with prolactin, 17ß-estradiol, progesterone, and hydrocortisone did not modify the susceptibility to proteolysis. However, after heat denaturation, cytosol proteins of regressing and growing tumors became equally susceptible to proteolysis. It is suggested that regression of MTW9 mammary carcinoma occurs not only because cell reproduction is arrested, but also because susceptibility of cytosol proteins to proteolysis is increased.

¹ Part of this work has been presented at the Annual Meeting of the American Association for Cancer Research, May 6 to 8, 1976, Toronto, Ontario, Canada (28). This is Paper 8 in a series on mammary tumor regression from the Laboratory of Pathophysiology, National Cancer Institute, NIH, Bethesda, Md.

² Recipient of a Fellowship from Le Conseil de la Recherche en Santé du Québec in 1974 and 1975.

³ To whom requests for reprints should be addressed.

Received 9/ 7/76. Accepted 12/ 2/76.