Breast cancer [electronic resource] : dietary links to gland and tumor development and effects of genistein and a-lactalbumin on primary tumors in vitro /

by Hudson, Elizabeth Jane

Hudson, Elizabeth Jane. Breast Cancer: Dietary Links to Gland and Tumor Development and Effects of Genistein and ?-Lactalbumin on Primary Tumors in vitro (Under the direction of Dr. Brenda Alston-Mills.) Nutrients found in foods have been shown to affect the occurrence of some types of cancer whereby they modulate hormone secretion, and have short-term impacts on reproductive organs and long-term impacts on the development of tumors in those tissues. Many types of food and nutrients in those foods have been shown to contribute by being a causative factor in tumor cell development. However, there are several foods that may have an opposite effect by serving as a source of cancer prevention or treatment. The whey milk protein, ?-lactalbumin (?-LA) has been shown to inhibit growth of certain mammary tumor cell lines in vitro. Soy contains the isoflavone genistein, which in some cases, has also been shown to contribute to the prevention and occurrence of breast cancer. Cell lines provide some information but little work has been done using primary mammary tumor tissue. Some foods, i.e. soy, enhance the developmental process of the mammary gland resulting in accelerated maturity, leaving the gland less susceptible to tumor development. The objectives of this study were: 1) to determine the implications of nutrients in soy, skim, and casein-based diets at enhancing the maturity of the mammary gland in vivo and as a result the effects on tumorigenesis, and 2) to determine the effectiveness of ?-LA or genistein in inhibiting further growth of primary mammary tumor tissue cultured in vitro for 48hrs. The end result could lead to future treatments or dietary recommendations that may reduce incidence of breast cancer. Mammary gland tissue from 21 female rats fed either a soy, skim, or casein-based diet were collected at d52 and analyzed for cell proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemistry assay and amounts of the extracellular matrix protein, tenascin (TN), also by immunohistochemistry. The level of cell proliferation is linked to the maturity of the gland. A high level of cell proliferation is associated with an immature mammary gland, which is more susceptible to tumor development, and a low level of cell proliferation is associated with a more mature gland and less susceptible to tumor development. The carcinogen, 7,12-dimethylbenz-(a)anthracene (DMBA), which induces mammary tumor development, was administered to the remaining 20 rats at d 53. Once tumors developed, both mammary gland and tumor tissue were collected and analyzed for PCNA values and amounts of TN present. In addition, tumor samples were also cultured for 48hr with 0, 10, 50, 100, 500, or 1000 ng/ml of ?-LA or 0, 1, 10, 50, or 100µg/ml of genistein. Results showed diet to significantly affect the stage of development for mammary gland tissue in this study. The casein-fed animals had much higher levels of PCNA than found in mammary gland tissue of soy or skim-fed animals from the pre-DMBA group. A significant difference was also found between rats fed soy, skim or casein based diets with respect to tumor incidence. The soy group had more tumors to develop than the casein or skim groups. After a 48hr culture of tumor samples with ?-LA or genistein, no significant differences were found between the treatments or among treatment concentrations. However, an overall significant negative correlation between PCNA and TN levels in tumor tissue post culture was found. Breast Cancer: Dietary Links to Gland and Tumor Development and Effects of Genistein and ?-Lactalbumin on Primary Tumors in vitro by Elizabeth Jane Hudson A thesis submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the degree of Master of Science Nutrition Raleigh 2003