Specific binding and growth-promoting activity of insulin in endometrial cancer cells in culture.
OBJECTIVE
Insulin is known to be mitogenic to a variety of cells in culture. The purpose of this study was to investigate the possible role of insulin in the growth and development of endometrial cancers.


METHODS
Specific binding and growth effects of insulin were studied in 5 different human endometrial cancer cell lines derived from cancers with different degrees of differentiation: HEC-1-A and HEC-1-B (from a moderately well-differentiated adenocarcinoma), RL95-2 (from a moderately well-differentiated adenosquamous carcinoma), KLE (from poorly differentiated carcinoma), and AN3 CA (from a metastatic undifferentiated endometrial carcinoma). The receptors were further characterized by competitive binding and chemical cross-linking studies.


RESULTS
Binding studies with 125I-insulin revealed the presence of high-affinity binding sites for insulin on all the 5 cell lines. Binding of insulin was found to be highly specific. Competitive binding studies with 125I-insulin revealed that insulin was most effective in displacing the labeled hormone, whereas insulin-like growth factor-I and insulin-like growth factor-II competed for binding only at very high concentrations. Scatchard analysis of the binding data revealed that the association constant for the high-affinity binding sites ranged from 0.72 to 1.91 x 10(9) L/mol. Estrogen-receptor-negative cell lines HEC-1-A and HEC-1-B had the highest number of insulin receptors, whereas the estrogen-receptor-positive cell line RL95-2 had the least number of receptors. The effect of insulin on cell proliferation was studied by monitoring cell number and incorporating [3H]thymidine into deoxyribonucleic acid of the cells. Insulin stimulated cell growth of all the cell lines.


CONCLUSIONS
The results of this study indicate the potential role of hyperinsulinemia in the growth and development of endometrial cancer.
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555, USA.
M
M
Nagamani
C A
CA
Stuart
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003432:Cross-Linking Reagents; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000633:toxicity*; D008934:Mitogens / Q000378:metabolism / Q000633:toxicity*; D011869:Radioligand Assay; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D007328:Insulin; D008934:Mitogens