Insulin exerts direct effects on carcinogenic transformation of human endometrial organotypic cultures.
Epidemiological studies suggest an association between elevated insulin levels and endometrial cancer. We studied the effects of insulin on normal endometrial cell proliferation with cytotoxicity assays. Organotypic cultures were used to determine the effects of insulin on the development of malignant histological features and anchorage independent growth. Western Blots were used to analyze the mitogen-activated protein kinases and AKT pathways. We found that insulin exerts direct effects on endometrial cells by increasing proliferation and promoting carcinogenesis. Our results suggest that this occurs through ERK 1/2 and glycogen synthase kinase-3β Ser9 phosphorylation.
1Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, University of Oklahoma , Oklahoma City, Oklahoma , USA;
Erin A
EA
Bishop
Stan
S
Lightfoot
Elangovan
E
Thavathiru
Doris Mangiaracina
DM
Benbrook
D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008954:Models, Biological; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000187:drug effects; D046509:Tissue Culture Techniques
D007328:Insulin