Regulation of insulin binding to human mammary carcinoma

In vitro binding of labeled insulin was measured in crude membrane fractions of tumor and fat obtained at the time of breast cancer surgery in 23 women. There was significant insulin binding in 22 of 23 tumor specimens and in all 23 fat samples. High-affinity binding sites were present in tumors [Ka = 1.38 +/- 0.88 (S.E.) x 10(9) M-1 and adjacent fat membranes (Ka = 1.12 +/- 0.15 x 10(9) M-1]. The level of insulin binding was not related to either estrogen receptor status or tumor histological grade. There was a significant negative correlation between insulin binding to fat membranes and fasting insulin levels. In contrast, there was no significant relationship between insulin binding to tumor tissue and serum insulin levels, suggesting the loss of the capacity to "down-regulate" insulin-binding sites by breast tumor cells. The absence of this ability to regulate insulin-binding capacity could result in an increased sensitivity of breast tumor cells to the stimulatory effects of insulin.