Nuclear hormone receptor variants: their role in malignancy and progression to hormone resistance in cancer.

Structural variants of nuclear hormone receptors have been found in tumour tissues. Experimental evidence suggests two ways in which these variants may have oncogenic potential: 1. by suppressing the action of the normal hormone receptor, thereby acting as dominant negative oncogenes; 2. by activating hormone-responsive genes in a hormone-independent manner. These mechanisms may not only contribute to oncogenesis but also to the development of hormone resistance in tumours, e.g. breast and prostate cancer.