HORMONE RESISTANCE IN CANCER - THE ROLE OF ABNORMAL STEROID-RECEPTORS

Breast tumors that have become resistant to endocrine therapy have bee n found to contain estrogen receptor (ER) variants due to aberrant spl icing mechanisms of the ER gene. Exon skipping can give rise to domina nt-positive receptors that are transcriptionally active in the absence of estrogen, or dominant-negative receptors that are themselves trans criptionally inactive but prevent the action of the normal receptor. E R splice variants similar to those in breast cancer have also been rep orted 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 rec eptor (GR) cause resistance to cell lysis by dexamethasone. Thus, ther e is increasing evidence that mutations in the genes of steroid recept ors can cause loss of hormone dependency in different cancer types.