Receptor tyrosine kinases and their hormonal regulation in uterine leiomyoma.
Uterine leiomyomas (fibroids, myomas) are benign tumors that develop from smooth muscle cells. Although the most common gynecologic tumor in premenopausal women, there is still little known of the etiology, the genetics and basic/molecular biology, or the influence of the environment on the development and growth of these tumors. The fact that fibroids occur during the reproductive years and regress after menopause indicates a growth dependent on ovarian hormones. Studies have supported a role of estrogen and progesterone in leiomyoma growth possibly through regulating growth factors and their signaling pathways. Activation of steroid hormone receptors can have a myriad of effects and include upregulation of growth factors and receptor tyrosine kinases (RTKs), which through downstream effector proteins such as mitogen-activated protein kinase p44/42, can mediate transcription, translation, and cell proliferation. Due to their hormonal dependency, fibroids may also be targeted by environmental chemicals whose biological effects are mediated through the estrogen and/or progesterone receptors. This review focuses on the role of growth factors and their receptors (RTKs) in uterine leiomyoma growth and their regulation by ovarian hormones. It also presents data on specific signaling pathways activated in uterine leiomyomas and the "cross talk" between the estrogen receptor alpha and RTK signaling pathways.
Yu
Linda
L
Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
Moore
Alicia B
AB
Dixon
Darlene
D
D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D020239:Receptor Cross-Talk; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction; D014594:Uterine Neoplasms / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D004967:Estrogens; D006728:Hormones; D011374:Progesterone; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D020928:Mitogen-Activated Protein Kinases