title: Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy.
abstract: Uterine leiomyomas are the most common tumors of the female genital tract, affecting 50% to 70% of females by the age of 50. Despite their prevalence and enormous medical and economic impact, no effective medical treatment is currently available. This is, in part, due to the poor understanding of their underlying pathobiology. Although they are thought to start as a clonal proliferation of a single myometrial smooth muscle cell, these early cytogenetic alterations are considered insufficient for tumor development and additional complex signaling pathway alterations are crucial. These include steroids, growth factors, transforming growth factor-beta (TGF-β)/Smad; wingless-type (Wnt)/β-catenin, retinoic acid, vitamin D, and peroxisome proliferator-activated receptor γ (PPARγ). An important finding is that several of these pathways converge in a summative way. For example, mitogen-activated protein kinase (MAPK) and Akt pathways seem to act as signal integrators, incorporating input from several signaling pathways, including growth factors, estrogen and vitamin D. This underlines the multifactorial origin and complex nature of these tumors. In this review, we aim to dissect these pathways and discuss their interconnections, aberrations and role in leiomyoma pathobiology. We also aim to identify potential targets for development of novel therapeutics.
authors: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, United States of America.|Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, Texas, United States of America.
authors: Mostafa A
authors: MA
authors: Borahay
authors: Department of Obstetrics and Gynecology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors: Ayman
authors: A
authors: Al-Hendy
authors: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors: Gokhan S
authors: GS
authors: Kilic
authors: Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, Texas, United States of America.
authors: Darren
authors: D
authors: Boehning
mesh_terms: D000818:Animals; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007889:Leiomyoma / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D013256:Steroids