报告题目： Maternal Obesity-Inducing High Fat Diet (OIHF) and the Risk of Breast Cancer Recurrence in the Female Offspring
报告摘要: Almost half of African American women at a childbearing age are obese, and the incidence is 27% higher than in Caucasian women. Using a preclinical model, we studied if maternal obesity affects the age when female offspring develop mammary cancer and the risk of breast cancer recurrence; both of which are different in African American women. We found a non-significantly earlier onset of mammary cancer, initiated with a carcinogen 7,12-dimethylbenz[a]anthracene (DMBA), and a three-fold higher risk of recurrence after completing of an equivalent of 5 years of tamoxifen (TAM) therapy in the offspring of dams fed obesity-inducing high-fat (OIHF) diet before and during pregnancy. Maternal OIHF diet activated unfolded protein response (IRE1α and eIF2α) and interacting inflammation (PKR, PACT, IRS1 and IKKα/β) pathways in the offspring’s mammary glands. In the tumors of OIHF offspring, autophagy was induced (increased Beclin 1) before TAM therapy, and then disrupted by TAM therapy (p62 and NBR1 accumulated), compared with tumors in the controls. In addition, in the TAM treated tumors of OIHF offspring, VEGFR2 and TGFβ1 expression was higher and the number of CD8+ and Granzyme B+ (GZMB) cells was reduced, indicative of reduced anti-tumor immunity and increased ability to escape tumor immune-surveillance. These findings suggest that maternal overweight may pre-program daughters to have increased breast cancer recurrence, perhaps through mechanisms that involve disruption of tumor autophagy and immune responses. Whether maternal obesity explains racial disparity in breast cancer remains to be studied.
报告人简介：张夕原，美国国立卫生研究院国家癌症研究所博士后。2009年毕业于上海交通大学食品科学与工程专业，获得本科学位。2011年获美国伊利诺伊大学香槟分校（UIUC）人类营养科学专业硕士学位。2016年获得乔治城大学医学研究中心( Georgetown University Medical Center )的博士学位。自2016年起在美国国立卫生研究院国家癌症研究所从事博士后研究。长期从事面向临床的营养学及肿瘤研究，近年研究成果发表在Clinical Cancer Research.等期刊发表研究论文共计13篇。
1. Xiyuan Zhang,Katherine Cook, Anni Warri, Mariana Rosem, Idalia Cruz, Jeffrey Riskin, William Helferich, Daniel Doerge, Robert Clarke and Leena Hilakivi-Clarke. Genistein intake prevents mammary cancer recurrence in tamoxifen-treated rats and improves tumor immunoediting.Clinical Cancer Research.2017 Feb 1;23(3):814-824. doi: 10.1158/1078-0432.CCR-16-1735.
2. Zhang X, Zhou D, Strakovsky RS, Zhang Y, Pan YX. Hepatic Cellular Senescence Pathway Genes Are Induced Through Histone Modifications In A Diet-Induced Obese Rat Model.Am J Physiol Gastrointest Liver Physiol.2012 Mar 1;302(5):G558-64.
3. Zhang X, Strakovsky R, Zhou D, Zhang Y, Pan YX. A Maternal High-Fat Diet Represses the Expression of Antioxidant Defense Genes and Induces the Cellular Senescence Pathway in the Liver of Male Offspring Rats.J Nutr.2011 Jul; 141(7):1254-9.