Anil Kaul
Oklahoma State University, USA
Title: Possible role of estrogen receptors in gender susceptibility in the development of chronic infections and liver cancers
Biography
Biography: Anil Kaul
Abstract
Studies have shown that there is a sex bias in the development of chronic infections that might lead to malignant transformation. Host immune responses in women with different levels of hormones such as estrogen have an influence on urinary tract infections. However, at present there is very limited understanding of contribution of hormones such as estrogen or its receptors (ERs) in modulating host-pathogen interaction in infectious disease pathogenesis. We studied estrogen and ER in their modulation of bacterial or viral pathogenesis in the liver. Hepatitis C virus (HCV) related cirrhosis is the prime cause of rising incidence of hepatocellular carcinoma (HCC). Chronic HCV progresses more rapidly in men than women. Predominance of HCV-related HCC in males highlights possible significance of estrogen related etiology in HCC. Role of estrogens and ERs is poorly understood in HCV related HCC pathogenesis. We studied liver tissues including HCV cirrhotic, HCV-related HCC (HCC) and normal donor explant livers for the expression of ERs (ERα and ERβ) at mRNA and protein level. ERα and ERβ co-expressed differentially at mRNA and protein levels in all groups. Sub-cellular distribution of ERα and ERβ protein levels were determined in cytosolic and nuclear fractions of normal, HCV and HCC tissues. Compared to normals, a significant increase in cytosolic levels of ERα was observed in HCV and HCC tissues. However, compared to normals, the nuclear expression of ERα was increased only in HCV and HCC patients. Higher nuclear expression of ERα in HCV and HCC suggests involvement of ERα in HCV associated HCC. Further studies on the role of estrogen and ERs involvement in HCV-related HCC pathogenesis may help us develop novel therapeutic approaches against HCC development.