Alcohol, obesity, and estrogen regulate mammary tumorigenesis through adiposity and the PI3K/Akt signaling pathway

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Title: Alcohol, obesity, and estrogen regulate mammary tumorigenesis through adiposity and the PI3K/Akt signaling pathway
Author: Hong, Jina
Abstract: Breast cancer is the most common cancer and the second leading cause of cancer deaths among women in the United States . Alcohol consumption increases breast cancer risk in women . It is unclear whether the effects of alcohol on mammary tumorigenesis are modified by body weight or exogenous estrogen . To determine if the effects of alcohol on mammary tumors are modified by body weight , mice of different body weights (lean , overweight , obese ) consuming water or alcohol were injected subcutaneously with mammary cancer cells . To determine if the effects of alcohol on mammary tumors are modified by estrogen , pellets delivering estrogen were implanted into female mice , followed by subcutaneous mammary cancer cell injections . Results show that alcohol -consuming mice were more insulin sensitive and developed larger tumors sooner than water -consuming mice (p <0 .05 ) . Our data show obese mice developed larger tumors than lean mice . Exogenous estrogen triggered the loss of body fat , induced insulin sensitivity , and suppressed tumor growth . Obese mice had higher levels of insulin , IGF -1 , leptin , and VEGF . The only mammary tumor growth factors increased by alcohol consumption were leptin and VEGF (p <0 .05 ) . In addition , activation of the PI3K /Akt signaling pathway was induced by alcohol and obesity in mammary tumors . Furthermore , alcohol increased the invasiveness of breast cancer cells in a dose -dependent manner , but also decreased a metastasis suppressor gene Nm23 . Collectively , my dissertation suggests that alcohol consumption , obesity , and estrogen treatment regulate mammary tumorigenesis through hormones associated with adipose tissues and the PI3K /Akt signaling .
URI: http : / /hdl .handle .net /2152 /ETD -UT -2010 -05 -1264
Date: 2011-01-10

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Alcohol, obesity, and estrogen regulate mammary tumorigenesis through adiposity and the PI3K/Akt signaling pathway. Doctoral dissertation, University of Texas at Austin. Available electronically from http : / /hdl .handle .net /2152 /ETD -UT -2010 -05 -1264 .

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