Milk is a fluid produced by lactating mammals. The physiological role of milk is to provide substances important to the nutrition, development and growth of the mammalian newborn. The growth promoting activity of milk may be due in part, to the presence of growth factors, mitogens capable of stimulating DNA synthesis and cell division in cultured cells. Such growth factors have been found in human, bovine, sheep, and mouse milk. We have identified a new growth factor present in the milk of mice which spontaneously develop mammary cancer. This factor is not only present in the milk from mice with a palpable tumor, but is also found in milk samples prior to the development of a clinically detectable tumor. In preliminary studies the presence of this growth factor in milk samples was predictive of which mice would subsequently develop mammary tumor. Milk was obtained from substrains of mice with high (greater than 90%) and low (less than 30%) mammary tumor incidence and also from control mice (less than 1% mammary tumor incidence). Milk samples were fractionated by HPLC using a size exclusion column. Lyophilized HPLC fractions were tested for mitogenic activity with an in vitro proliferation assay measured by 3H-thymidine incorporation. Though HPLC protein profiles of all milk samples were virtually identical, the presence of this new growth factor (12K) was substrain dependent. It is important to note that human breast milk may also contain similar mitogenic activity in the 10-15K molecular weight range. As in our mouse model, this activity is not present in milk samples from every human donor. We propose to determine the presence and begin to characterize this growth factor activity in mice with mammary tumor and in those at risk of developing mammary tumors. We will determine if the presence of this growth factor is predictive of tumor development. In addition, we will explore the relationship between the growth factor in mouse milk and a similar growth factor in human milk. The isolation and the identification of such growth factors may lead to the development of a biological tumor marker which would help to identify women who are at an increased risk of developing breast cancer.
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