Hormone resistance in cancer: the role of abnormal steroid receptors.
Breast tumors that have become resistant to endocrine therapy have been found to contain estrogen receptor (ER) variants due to aberrant splicing mechanisms of the ER gene. Exon skipping can give rise to dominant-positive receptors that are transcriptionally active in the absence of estrogen, or dominant-negative receptors that are themselves transcriptionally inactive but prevent the action of the normal receptor. ER splice variants similar to those in breast cancer have also been reported in human meningiomas. Androgen receptor (AR) variants have been detected in some prostate cancers that exhibit resistance to androgen therapy. In leukemia and lymphoma, mutations in the glucocorticoid receptor (GR) cause resistance to cell lysis by dexamethasone. Thus, there is increasing evidence that mutations in the genes of steroid receptors can cause loss of hormone dependency in different cancer types.
Department of Tumor Biology, The Netherlands Cancer Institute, Amsterdam.
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D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012326:RNA Splicing; D011987:Receptors, Steroid / Q000187:drug effects* / Q000235:genetics / Q000502:physiology
D018931:Antineoplastic Agents, Hormonal; D011987:Receptors, Steroid