Membrane-associated phosphatidylinositol kinase of R3230AC mammary tumors and normal mammary glands and effects of insulin on tumor enzyme activity.
Phosphatidylinositol (PI) kinase was characterized, its activity was measured in plasma membrane-enriched fractions of R3230AC rat mammary tumors, and these results were compared to enzyme activity in normal mammary glands at various stages of differentiation. PI kinase activity was found to be highest in mammary adenocarcinomas, whereas the mammary gland displayed the following order of decreasing activity: late lactation greater than early lactation greater than late pregnancy. Although diabetes only slightly increased tumor membrane PI kinase activity, insulin treatment of tumor-bearing diabetic rats, which reduced R3230AC tumor growth, caused a significant reduction (30 to 40%) in PI kinase activity. These results imply that PI kinase activity may be correlatable with normal mammary gland differentiation and with mammary tumor growth behavior. Formation of phosphatidylinositol-4-phosphate in tumor membranes was inhibited by low concentrations of calcium (microM range), suggesting the presence of calcium-sensitive polyphosphoinositide metabolism in the R3230AC carcinoma.
Narayanan
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U
Department of Biochemistry, University of Rochester School of Medicine and Dentistry, New York 14642.
Keuker
C
C
Hilf
R
R
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D005260:Female; D007328:Insulin / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000201:enzymology*; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344
D007328:Insulin; D010716:Phosphatidylinositols; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D002118:Calcium