title: Genes involved in the immediate early response and epithelial-mesenchymal transition are regulated by adipocytokines in the female reproductive tract.
abstract: Obesity increases the risk of female reproductive tract cancers, but the underlying mechanistic link between the two is ill-defined. Thus, the objective of the current study was to identify obesity-dependent changes in the expression of immediate early (IE) genes that contribute to cell proliferation and differentiation, and epithelial-mesenchymal transition (EMT) genes that promote cell migration. When HeLa cells were treated for 0-48 hr with IGF-1, leptin, TNFα, or IL-6, each individual adipocytokine altered the abundance of IE (cJUN, cFOS, and cMYC) and EMT (SNAI1, SNAI2, and TWIST1) mRNA abundance. For example, IGF-1 increased cJUN and cFOS and decreased cMYC; leptin increased cFOS; IL-6 increased cFOS and cMYC; and TNFα increased cJUN and cFOS mRNA abundance. Likewise, EMT gene expression was altered by IGF-1, TNFα, and IL-6. SNAI1 was increased by IGF-1 and IL-6; SNAI2 was increased by IGF-1 and TNFα; and TWIST1 was increased by TNFα and IL-6. Chronic exposure to adipocytokines also altered EMT gene expression in the whole uterus of obese compared to normal-weight mice. Specifically, there was no difference in cJun, cFos, or cMyc mRNA abundance between normal-weight and obese animals. Snai1, Snai2, and Twist1 mRNA abundance, however, was increased in the uterus of obese females and correlated with increased circulating IGF-1 levels. These data indicate that obesity-dependent alterations in adipocytokine levels regulate the expression of genes associated with cell proliferation and migration, and therefore may provide a plausible mechanism for obesity-dependent increases in cancers of the female reproductive tract.
authors: Department of Animal Science, University of Nebraska-Lincoln, Lincoln, Nebraska 68583-0908, USA.
authors: Zhufeng
authors: Z
authors: Yang
authors: Kristin A
authors: KA
authors: Norwood
authors: Jacqueline E
authors: JE
authors: Smith
authors: Jill G
authors: JG
authors: Kerl
authors: Jennifer R
authors: JR
authors: Wood
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D017781:Genes, Immediate-Early / Q000502:physiology*; D016762:Genes, fos / Q000502:physiology; D016758:Genes, jun / Q000502:physiology; D016259:Genes, myc / Q000502:physiology; D005836:Genitalia, Female / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D054392:Adipokines