Hormone dependence and estradiol receptors in the D series of mammary nodule outgrowth lines and tumors.

Preneoplastic mammary nodule outgrowth lines were examined for their ability to grow and produce tumors in ovariectomized BALB/c mice. In addition, these nodule outgrowth lines and tumors derived from them were investigated for cytoplasmic estrogen receptor proteins by qualitative and quantitative techniques. Early ovariectomy, performed within 4 weeks after transplantation, slightly delayed but did not permanently block the ability of three different nodule lines to completely fill the fat pad with nodule tissue. Ovariectomy performed later than 4 weeks after transplantation or adrenalectomy performed early or late had no effect on nodule growth. Neither early nor late ovariectomy or adrenalectomy had an effect on the maintenance of the nodule alveolar phenotype. Ovariectomy performed 3 weeks after transplantation had little effect on the tumor potential of the low oncogenic line D1 or the high oncogenic line D2. Samples of nodule outgrowths transplanted from ovariectomized mice responded to a chemical carcinogen in a similar manner, as did nodule outgrowths transplanted from control experiments. Thus, the altered hormonal environmenment in ovariectomized mice apparently did not select for subpopulations of nodule cells with altered tumorigenic potentials. The ovarian independence of the nodule lines and tumors derived from them was correlated with a very low level of cytoplasmic estrogen receptor. These results, along with other data, illustrate the nature of the independence on ovarian hormonal control for tumorigenesis in these mammary tumor virus-free nodule lines.