The Roles of Estrogen Receptors in the Bladder Cancer Development

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Pathology and Laboratory Medicine, 2013.Early studies documented the existence of sexual dimorphism in bladder cancer occurrence and progression with higher bladder cancer incidence in males than females. However, the progression of bladder cancer after diagnosis is more rapid in females than males. These contrasting differences could be due to the differential effects of female hormones-estrogens, and their binding receptors including ERα and ERβ on the bladder cancer incidence and progression. Results from recent studies using various in vitro cell lines and in vivo mouse models demonstrate differential roles of ERs in cancer initiation and progression such that ERα suppresses bladder cancer initiation and invasion whereas ERβ promotes bladder cancer initiation and progression. Mechanistic studies indicate ERα and ERβ may act through modulation of the AKT activity/pathway or DNA replication complex, respectively, to influence bladder cancer progression. Targeting ER signaling pathways using various selective ER subtype modulators may lead to the development of new therapeutic approaches to control bladder cancer progression