PREGNANCY ASSOCIATED PROTECTION AGAINST BREAST CANCER

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DESCRIPTION: (adapted from the investigator's abstract) Pregnancy provides significant protection against breast cancer development in women that give birth before the age of 20 years. Similarly, parous rats are refractory to chemically induced mammary tumorigenesis. The mechanisms by which parity affects mammary cancer incidents will be investigated by the investigator and coworkers in this proposal using the rat as a model. Pregnancy is characterized by elevated concentrations in serum of hormones that regulate the development of the mammary gland and affect mammary carcinogenesis. This proposal examines the hypothesis that these hormonal changes, along with changes in the levels of hormone and growth factor receptors in the mammary gland, played a decisive role in reducing mammary gland susceptibility to carcinogenesis. In specific aim I, mammary tissue and isolated mammary epithelial cells from virgin rats previously treated with carcinogen, which are highly susceptible carcinogenesis, will be transplanted into gland-free pads of parous hosts, which are refractory to carcinogenesis, and vise versa to determine whether refractory mammary tissue becomes susceptible and if susceptible mammary tissue become refractory to carcinogenesis in an appropriate hormonal environment. In addition, isolated mammary tumor cells will be transplanted into gland-free fat pads of refractory and susceptible rats to determine whether the hormonal environment of both these groups of rats is capable of sustaining the growth of already established mammary tumors. In specific aim II, the role of growth hormone (GH), prolactin (PRL) and ovarian steroids in mediating the parity-associated refractoriness to chemically induced carcinogenesis will be examined. Somatostatin analog and bromocriptine will be used to reduce the circulating concentrations of GH and PRL, respectively, in virgin rats to the concentrations in parous rats. GH and PRL will be administered in osmotic pumps to parous rats to obtain the concentrations in serum of virgin animals. The GH and PRL manipulations will be carried out in intact rats and ovariectomized animals, untreated or treated with constant dosage of 17beta-estradiol and/or progesterone. All these experimental groups and untreated control groups will be injected with carcinogen and tumor incidence compared.