Hormones and hormone antagonists: mechanisms of action in carcinogenesis of endometrial and breast cancer.
Proliferation of breast and endometrial cells is under the control of ovarian steroid hormones (SHs) such as oestrogen and progesterone. They mediate diverse physiological functions via interaction with nuclear-localised steroid hormone receptors (HRs). The SH receptor complex modifies the expression of SH-regulated genes by binding to conserved binding sites in their promoter region or through cross-talk with other transcription factors. In non-malignant tissues, HRs are in balance with other factors regulating proliferation, differentiation and apoptosis. While dysfunction of the regulatory mechanisms is a part of malignant transformation, functional SH receptors can promote growth of SH-responsive tumours. Therefore, anti-hormones that block the interaction of steroid hormones with the SH receptor are useful tools for the treatment of SH-responsive carcinomas. However, a portion of ER-positive breast cancers and most endometrial cancers do not respond to anti-oestrogens and continued treatment results in hormone resistance, mostly without loss of the ER. This review focuses on the mechanisms of action of hormones and anti-hormones in breast and endometrial carcinomas.
Flötotto
T
T
University Hospital Düsseldorf, Department of Obstetrics and Gynaecology, Düsseldorf, Germany.
Djahansouzi
S
S
Gläser
M
M
Hanstein
B
B
Niederacher
D
D
Brumm
C
C
Beckmann
M W
MW
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020847:Estrogen Receptor Modulators / Q000378:metabolism* / Q000627:therapeutic use; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006727:Hormone Antagonists / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D006801:Humans; D020239:Receptor Cross-Talk / Q000502:physiology; D011960:Receptors, Estrogen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D020847:Estrogen Receptor Modulators; D004967:Estrogens; D006727:Hormone Antagonists; D006728:Hormones; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D013256:Steroids; D014157:Transcription Factors