A Tale of Breast Cancer, Behavior and Brains as Affected by Diet and Claudins
The purpose of this research is to explore mammary gland development and reproductive behavior from a new perspective by combining information obtained from various treatment interventions. Specifically, the expectation is to provide new insights on the holistic effects of dietary intervention throughout the span of mammary gland development. Dietary studies in rats suggest that soy and skim milk diets can prolong latency and reduce chemically induced tumorigenesis in the mammary glands. Further, studies have shown that alteration in the cross talk between the glandular epithelium and the extracellular matrix are correlated to cancer risk. While positive effects are reported on the development of the gland, contrasting effects of soy and isoflavones are observed in the libido of adult female rats. In contrast, the whey milk protein, alpha-lactalbumin (?-LA) enriched diets induce beneficial effects on mood by inducing anxiolytic-like and rewarding effects in rats. Furthermore, tight-junction proteins, claudins 4 and 7 have been recently shown to be biomarkers of metastasis. As a model for breast cancer the her2/neu transgenic mouse was used. At day 21, weaned mice were placed on one of four isocaloric and isoproteinacuos diets(n=12/grp): 1) casein (negative control); 2) soy, ?-LA, soy and ?-LA, casein plus estradiol benzoate (EB) injection (positive control) or ?-LA + EB. These groups were sampled at postnatal day 28. Evaluations of changes in the glandular epithelium were conducted using wholemount analysis. In the behavioral study component, females were exposed to sexually mature males for evaluation and comparison of changes in reproductive interest via measures of caudal and rostral proximity, line crossing, and neurochemistry.
Proteins were extracted and analyzed using the enzyme linked immunnosorbant assay (ELISA). Wholemount analyses of the inguinal glands were made to assess morphological changes after 7 days of treatment. Neurochemical changes in the brain were performed by immunohistochemistry IHC. The ultimate goal was to establish a link between behavior and mammary glandular responses as a function of treatment. We have shown that treatment can, both directly and indirectly, alter mammary gland architecture. Results demonstrate that the L treatment is the greastest promoter of MFPi. The Soy treatment exerts an estrogenic effect on the MFPi and does not attenuate the L effect when consumed in combination, while the E treatment does attenuate the effect of L. Moreover, Estrogen treatment was found to have the highest distribution of ABs across treatments (71.5) while the Soy treatment was found to have the second highest rating among treatments. Interestingly when in combination with S or E the effect of L decreased. The distribution of TEBs was effected greatest by estrogen also. Lactalbumin when in combination with E has the highest distribution among treatments. While S and L alone seem to have similar effects on TEB distribution, when consumed in combination they synergize to have an estrogenic affect. This duality in treatment response is further represented in the reproductive behavior outcomes. From the vaginal smear analysis it is obvious that the L treatment alone is acting estrogenically (91% positive for sperm). In contrast, when the L treatment is consumed in combination with E or S there is either slight attenuation (83% positive for sperm) or complete ablation (0% positive for sperm) of the effect. Uterine weight was affected the most by the treatment that consisted of the EL combination. Moreover, L had the greatest effect on Caudal and Rostral proximity. It is clear that holistic diet treatment can alter mammary gland architecture and other reproductive parameters throughout the span of development.
Advisor:Brenda Alston-Mills; Brenda Judge Grubb; Heather Patisaul
School:North Carolina State University
School Location:USA - North Carolina
Source Type:Master's Thesis
Date of Publication:06/12/2007