Schedule and Program - North Carolina Academy of Science

Endocrine Disrupting Chemicals Promote Ovarian Cancer Cell Growthvia the Estrogen Receptor-CXCL12 Signaling AxisJulie M. Hall and Kenneth S. KorachCampbell UniversityThe majority of human ovarian cancers over-express estrogen receptors (ER) and grow in response to estradiol(the endogenous estrogen). We previously demonstrated that ER up-regulation of the chemokine CXCL12 isrequired for estradiol-stimulated proliferation of human ovarian carcinoma cells. In the current study we reportthat known ‘endocrine disrupting chemicals’ (EDCs) stimulate growth of ovarian cancer cells via their abilityto activate the ER and up-regulate CXCL12 expression. Notably, the EDCs genistein, bisphenol A and HPTEstimulated both cell proliferation and induction of CXCL12 mRNA and protein in a manner comparable toestradiol. The effects were completely attenuated by the ER antagonist ICI 182,780, revealing that observedactivities of these agents were receptor-mediated. In cell proliferation assays the mitogenic effects of estradioland EDCs were obviated by siRNAs targeting CXCL12 and restored upon addition of exogenous CXCL12.Furthermore, an inhibitor to the CXCL12 receptor CXCR4 completely attenuated growth-stimulatory effectsof estradiol and EDCs. These studies highlight a potential role of EDCs possessing estrogenic activities in theetiology of ovarian cancer. Moreover, they suggest that the ER-CXCL12-CXCR4 signaling axis may represent apromising target for development of therapeutics for ER+ ovarian cancers.Epigenetic Regulation of Histone-H3 (H3) by MAPK44/42 via MSK-1by GenisteinKyle Ham*, Linda Yu, Lysandra Castro, Alicia B. Moore, and Darlene DixonMount Olive CollegeUterine leiomyomas (fibroids) are benign tumors of smooth muscle origin found in the human uterus. Thereis very little known about the etiology or pathogenesis of these tumors, although there is evidence that theyare hormonally regulated. Genistein, a phytoestrogen, is classified as an isoflavane, and has been shown tobind to human estrogen receptors, causing effects similar to estrogen. Immunohistochemical staining wasused to determine the expression of phosphorylated and total MSK-1 and H3 in human uterine leiomyomaand myometrial tissues in the proliferative phase of the menstrual cycle. Western Blotting was used to assessphosphorylated and total MAPK44/42, MSK-1, and H3 expression levels in immortalized (hTERT) UtLMand uterine smooth muscle cells (UtSMC) treated with genistein at concentrations of 1 ug/mL or 50 ug/mL.There appeared to be higher expression of phospho-MSK-1 and phosphorylated H3 in tumors compared tonormal myometrium. Genistein at 1 ug/mL increased phosphorylated MAPK44/42 and MSK-1 at 10 minand continued to 60 min, and H3 levels at 10 min in hTERT-UtLM cells. Genistein at 50 ug/mL increasedphosphorylated MSK-1 expression; however, it was nearly half of that observed in the low dose and did not resultin increased phosphorylation of H3. Additionally, increased expression of phosphorylated MSK-1 or H3 wasnot seen in hTERT-UtSMC cells. We have concluded that epigenetic changes through activation of MSK-1 andH3 might be one of the mechanisms involved in cell proliferation induced by genistein at 1 ug/mL as previouslyreported in UtLM cells.Fitness Effects of Reproductive Thermoregulatory Ability in Plantagolanceolata in different thermal environmentsFreddy O. Herrera, Elizabeth P. Lacey, and Scott J. RichterUniversity of North Carolina at GreensboroUnderstanding the role of thermoregulatory ability in nature can provide important information about its potentialin buffering the effects of climate change in ectotherms. I am conducting manipulative transplant experiments usingPlantago lanceolata genotypes that vary in thermoregulatory ability. P. lanceolata can partially thermoregulate its50 - NC Academy of Science