Narayanan U, Keuker C, Hilf R
Department of Biochemistry, University of Rochester School of Medicine and Dentistry, New York 14642.
Cancer Res. 1988 Dec 1;48(23):6727-32.
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.
对磷脂酰肌醇（PI）激酶进行了特性分析，测定了其在R3230AC大鼠乳腺肿瘤富含质膜的组分中的活性，并将这些结果与不同分化阶段正常乳腺中的酶活性进行了比较。发现PI激酶活性在乳腺腺癌中最高，而乳腺的活性呈现以下递减顺序：泌乳后期＞泌乳早期＞妊娠后期。虽然糖尿病仅轻微增加肿瘤膜PI激酶活性，但用胰岛素治疗荷瘤糖尿病大鼠（这会减少R3230AC肿瘤生长）会导致PI激酶活性显著降低（30%至40%）。这些结果表明，PI激酶活性可能与正常乳腺分化以及乳腺肿瘤生长行为相关。低浓度钙（微摩尔范围）可抑制肿瘤膜中磷脂酰肌醇-4-磷酸的形成，提示R3230AC癌中存在钙敏感的多磷酸肌醇代谢。
