Steroid hormone receptor signaling in cancer.
SHRs function as hormone activated, sequence specific DNA binding transcription factors that recruit multiple coactivator and other proteins to specific genes and generally stimulate transcription of these genes. SHR may have further genomic actions, that do not involve direct DNA binding, through protein-protein interactions with other sequence specific transcription factors, although these may still involve weak binding to nonconsensus steroid responsive elements in vivo. SHRs also appear to have nongenomic effects mediated through interactions with cytoplasmic signaling proteins. The major functions of SHRs in normal adult tissues appear to involve stimulation of differentiation, rather than proliferation. In contrast, the ER alpha and AR directly stimulate the growth of breast and prostate cancers, respectively, indicating a critical change in their functions. The ER alpha and AR appear to undergo further adaptation in tumor cells in response to hormonal therapies, that render these therapies ineffective. Understanding the molecular basis for these changes in SHR function during cancer development and progression may provide new targets for the generation of drugs to prevent and treat steroid stimulated cancers.
Cheng
Shinta
S
Cancer Biology Program, Hematology-Oncology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Balk
Steven P
SP
D000818:Animals; D005260:Female; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000378:metabolism*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction
D006728:Hormones; D011956:Receptors, Cell Surface