The objective of the current study is to investigate the effect of maternal high fat diet and changes in metabolic bioenergetics on prostate gland development and susceptibility to prostate cancer in the male offspring. We hypothesize that a high fat maternal diet prior to and throughout pregnancy alters epigenomic marks leading to abnormal expression of key genes involved in the development of the prostate gland, which predispose the offspring to develop prostate cancer. Our rationale is that if maternal diet and metabolic bioenergetics alter the process of tumor development and progression in the prostate, then further studies exploring the mechanism of this process may elucidate new therapies and recommendations for the prevention and treatment of prostate cancer. To test our hypothesis the following aims will be pursued:
Specific Aim 1 : To examine prostate gland development and imprinted gene expression in control vs high fat fed offspring, from mothers given a high fat diet for 1 month prior to conception and throughout pregnancy.+ Specific Aim 2: To examine the incidence and timing of tumor development in offspring of control vs high fat fed mothers by administration of diethylstilbestrol (DES) to neonatal male mice on postnatal days 1-5.
Specific Aim 3 : To examine the effects of a high fat diet on tumor development in an established model for prostate cancers. The high fat diet experiment will be performed in mice with prostate specific knockout of PTEN vs controls (Pten[loxp/lop];PB-Cre4*) vs Pten*'*;PBCre4-). This proposal is innovative in that although data show that dietary changes during pregnancy can result in epigenetic changes in the offspring and that some of these epigenetic changes have been linked to prostate cancer, the connection between maternal diet and prostate cancer has never been explored. It is anticipated that the maternal diet of high fat will accelerate this process and decrease the latency period to the development of cancer. If successful in complefing our aims this work will advance our understanding of how changes in maternal diet and metabolic bioenergefics in utero have transgenerational effects on the predisposition and development of prostate cancer.
|Ganti, Arun; Liu, Weijian; Luo, Suhong et al. (2014) Impact of body mass index on incidence of febrile neutropenia and treatment-related mortality in United States veterans with diffuse large B-cell lymphoma receiving rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone. Br J Haematol 167:699-702|
|Yaghjyan, Lusine; Wolin, Kathleen; Chang, Su-Hsin et al. (2014) Racial disparities in healthy behaviors and cancer screening among breast cancer survivors and women without cancer: National Health Interview Survey 2005. Cancer Causes Control 25:605-14|
|Fayanju, Oluwadamilola M; Kraenzle, Susan; Drake, Bettina F et al. (2014) Perceived barriers to mammography among underserved women in a Breast Health Center Outreach Program. Am J Surg 208:425-34|
|Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S (2014) Breast cancer risk accumulation starts early: prevention must also. Breast Cancer Res Treat 145:567-79|
|Sabounchi, Nasim S; Hovmand, Peter S; Osgood, Nathaniel D et al. (2014) A novel system dynamics model of female obesity and fertility. Am J Public Health 104:1240-6|
|Chang, Su-Hsin; Stoll, Carolyn R T; Song, Jihyun et al. (2014) The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003-2012. JAMA Surg 149:275-87|
|Yang, Lin; Hipp, J Aaron; Marx, Christine M et al. (2014) Occupational sitting and weight status in a diverse sample of employees in Midwest metropolitan cities, 2012-2013. Prev Chronic Dis 11:E203|
|Giammanco, Antonina; Blanc, Valerie; Montenegro, Grace et al. (2014) Intestinal epithelial HuR modulates distinct pathways of proliferation and apoptosis and attenuates small intestinal and colonic tumor development. Cancer Res 74:5322-35|
|Klos, Coen L; Safar, Bashar; Jamal, Nida et al. (2014) Obesity increases risk for pouch-related complications following restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). J Gastrointest Surg 18:573-9|
|Beason, Tracey S; Chang, Su-Hsin; Sanfilippo, Kristen M et al. (2013) Influence of body mass index on survival in veterans with multiple myeloma. Oncologist 18:1074-9|
Showing the most recent 10 out of 17 publications