Pathobiology Of Uterine Leiomyomas (fibroids)

Dixon, Darlene

Abstract

of Work: The Comparative Pathobiology Group has focused its research on defining the pathogenesis/carcinogenesis of disorders affecting the reproductive tract of humans and rodents, and assessing the role of environmental and endogenous factors in the induction of these disorders. Our group has used archival mouse and human tissues to determine the presence of growth factors in uterine leiomyomas (""""""""fibroids"""""""") and leiomyosarcomas in mice and women. Data from our studies show that TGF-a (mature form) is expressed exclusively in malignant uterine smooth muscle cell tumors (leiomyosarcomas) of mice. However, in benign uterine smooth muscle cell tumors (leiomyomas) of mice and women this growth factor is not present. In mice, we have also found a positive correlation between TGF-a staining and immunoexpression of epidermal growth factor receptor, and increased cell proliferation as measured by the expression of proliferating cell nuclear antigen (PCNA) in the malignant uterine leiomyosarcomas. Studies to assess the immunoexpression of factors (Bcl- 2; Bax) possibly modulating cell survival and death in human uterine leiomyomas show that both positive and negative regulatory proteins of programmed cell death (apoptosis) are present in uterine leiomyomas in women, and that apoptosis does not appear to play a significant role in the development of these tumors.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Environmental Health Sciences (NIEHS)
• Type: Intramural Research (Z01)
• Project #: 1Z01ES021196-08
• Application #: 6542231
• Study Section: (LEP)
• Support Year: 8
• Fiscal Year: 2001

Institution

• Name: U.S. National Inst of Environ Hlth Scis
• Country: United States

Publications

Tilley, Stephen L; Jaradat, Maisa; Stapleton, Cliona et al. (2007) Retinoid-related orphan receptor gamma controls immunoglobulin production and Th1/Th2 cytokine balance in the adaptive immune response to allergen. J Immunol 178:3208-18

Moore, A B; Castro, L; Yu, L et al. (2007) Stimulatory and inhibitory effects of genistein on human uterine leiomyoma cell proliferation are influenced by the concentration. Hum Reprod 22:2623-31

Dixon, Darlene; Parrott, Estella C; Segars, James H et al. (2006) The second National Institutes of Health International Congress on advances in uterine leiomyoma research: conference summary and future recommendations. Fertil Steril 86:800-6

Jaradat, Maisa; Stapleton, Cliona; Tilley, Stephen L et al. (2006) Modulatory role for retinoid-related orphan receptor alpha in allergen-induced lung inflammation. Am J Respir Crit Care Med 174:1299-309

Bauer, Alison K; Dixon, Darlene; DeGraff, Laura M et al. (2005) Toll-like receptor 4 in butylated hydroxytoluene-induced mouse pulmonary inflammation and tumorigenesis. J Natl Cancer Inst 97:1778-81

Hoffler, Undi; Dixon, Darlene; Peddada, Shyamal et al. (2005) Inhibition of urethane-induced genotoxicity and cell proliferation in CYP2E1-null mice. Mutat Res 572:58-72

Swartz, C D; Afshari, C A; Yu, L et al. (2005) Estrogen-induced changes in IGF-I, Myb family and MAP kinase pathway genes in human uterine leiomyoma and normal uterine smooth muscle cell lines. Mol Hum Reprod 11:441-50

Aoyama, Hiroaki; Couse, John F; Hewitt, Sylvia C et al. (2005) Upregulation of estrogen receptor expression in the uterus of ovariectomized B6C3F1 mice and Ishikawa cells treated with bromoethane. Toxicol Appl Pharmacol 209:226-35

Stapleton, Cliona M; Jaradat, Maisa; Dixon, Darlene et al. (2005) Enhanced susceptibility of staggerer (RORalphasg/sg) mice to lipopolysaccharide-induced lung inflammation. Am J Physiol Lung Cell Mol Physiol 289:L144-52

Nikitin, Alexander Yu; Alcaraz, Ana; Anver, Miriam R et al. (2004) Classification of proliferative pulmonary lesions of the mouse: recommendations of the mouse models of human cancers consortium. Cancer Res 64:2307-16