DNA synthesis of human, mouse, and rat mammary carcinomas in vitro: influence of insulin and prolactin

Carcinomatous mammary tissues, derived from six spontaneously arising mouse mammary tumors, six DMBA-induced rat mammary tumors, and 26 biopsy specimens of human breast tumors, were processed into slices and each tumor was inidvidually cultured for two days in Medium 199. The influence of bovine insulin (5.0 mug/ml) and ovine prolactin (10.0 mug/ml) on H3-thymidine incorporation into DNA was determined on the cultured tumor slices. Insulin consistenly (p less than 0.05-0.01) increased the incorporation of H3-thymidine into DNA of the organ cultures of mouse, rat, and human mammary carcinoma slices. The stimulatory effect of insulin was quantitatively more prominent in the mouse tumor slices than in the rat or human slices. The addition of prolaction to the insulin-containing culture medium further increased significantly (p less than 0.001) the incorporation of H3-thymidine into DNA of rat mammary carcinoma slices but had no significant effect on cultures of either mouse or human mammary carcinomas. The addition of prolactin to insulin and hydrocortisone-enriched medium containing slices of 20 individually cultured human breast carcinomas did not significantly influence the mean incorporation of H3-thymidine into DNA. However, a very small fraction (approximately equal to 15%) of these human breast carcinomas responded to prolactin by increasing the incorporation of H3-thymidine into DNA to a degree quantitatively comparable to the prolactin-sensitive, DMBA-induced rat mammary carcinoma. These results suggest that a very small fraction of human breast malignancies may respond to the growth-stimulatory effects of prolactin, but that the vast majority mimic more closely the prolactin-independent mouse mammary carcinoma.