Cell proliferation induced by insulin in organ culture of rat mammary carcinoma

Abstract

The effect of insulin on cell proliferation was investigated in carcinogeninduced, hormone-dependent mammary carcinomas of the rat in organ culture. Incorporation of 14C-thymidine into DNA was compared to other indices and appeared to provide a satisfactory estimate of cell proliferation in the explants. By using this parameter, it was found in 4-day cultures that insulin intensely stimulated cell proliferation in certain tumors. The effect was not apparent on the first day of culture, but developed from the second day on. Of 12 tumors studied in 2-day cultures, 5 showed a marked and significant increase in cell proliferation while the other 7 failed to show any change when insulin was added to the medium. The tumors that did not react to insulin had a high spontaneous rate of cell proliferation that could only be achieved in the other tumors by the stimulating action of insulin. These results seem to indicate that some tumors are dependent on insulin for growth in vitro while the others are independent. No morphological basis was found to account for this difference. It is suggested that loss of insulin dependence might represent a step in the process of tumor progression. Preliminary data indicating that insulin had little effect on glucose utilization by the explants are discussed.