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Regulation of normal and malignant prostate cell biology by IGF-I: mechanisms and modulation by dietary polyphenols and energy restriction

Wang, Shihua
http://rave.ohiolink.edu/etdc/view?acc_num=osu1054728791

Abstract Details

2003, Doctor of Philosophy, Ohio State University, Ohio State University Nutrition.
We hypothesize that energy intake / obesity may increase the risk of prostate cancer, in part, via increased IGF-I activity. Furthermore, we propose that dietary components in tomato and soy may inhibit IGF-I activity and subsequently reduce prostate carcinogenesis. The first study describes the characterization of an in vitro serum free media (SFM) system in which rat AT6.3 prostate cancer cell proliferation and survival are dependent on IGF-I. Using this model, we show that IGF-I stimulates cell proliferation and survival via intracellular signaling pathways including AKT and ERK1/2. Polyphenols from tomato and soy, such as genistein, biochanin A, daidzein, quercetin, kaempferol and rutin, demonstrate unique abilities to inhibit intracellular signaling pathways involving tyrosine kinase activity thereby reducing proliferation and enhancing apoptosis. We next examined gene expression profiles of AT6.3 cells treated with SFM with 10% fetal bovine serum (FBS), SFM alone, and SFM plus 50 ng/ml IGF-I using Affymetrix microarray technology. Our results demonstrate that IGF-I stimulates specific patterns of gene expression involving cell cycle control, proliferation, metabolism, apoptosis, angiogenesis, invasion and metastasis. Our results show that the ability of IGF-I to upregulate glucose uptake and glycolysis is essential for proliferation. We next examined the ability of diet restriction to alter gene expression profiles in the rat prostate. Affymetrix U34A Genechips and microarray technology were employed and our results demonstrate that dietary restriction modulates expression of many genes related to hormone receptors, cytokines, growth factors, nutrient metabolism, and xenobiotic metabolism. Our results suggest that DR modulates gene expression profiles of normal prostate tissue in a manner that may decrease carcinogenesis, in part, via reduced serum IGF-I. In summary, our studies suggest that IGF-I stimulates prostate cancer progression and that dietary factors increasing IGF-I activity, such as energy intake, may stimulate carcinogenesis, whereas dietary components such as polyphenols may reduce IGF-I activity and inhibit carcinogenesis.
Steven Clinton (Advisor)
298 p.
Health Sciences, Nutrition
IGF-I; dietary restriction; polyphenols; prostate; cancer; microarray; rats; cell signaling

Recommended Citations

Citations

  • Wang, S. (2003). Regulation of normal and malignant prostate cell biology by IGF-I: mechanisms and modulation by dietary polyphenols and energy restriction [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1054728791

    APA Style (7th edition)

  • Wang, Shihua. Regulation of normal and malignant prostate cell biology by IGF-I: mechanisms and modulation by dietary polyphenols and energy restriction. 2003. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1054728791.

    MLA Style (8th edition)

  • Wang, Shihua. "Regulation of normal and malignant prostate cell biology by IGF-I: mechanisms and modulation by dietary polyphenols and energy restriction." Doctoral dissertation, Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1054728791

    Chicago Manual of Style (17th edition)

osu1054728791
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© 2003, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.