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BACKGROUND Alterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal-cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway,(More)
The vertebrate retinoid X receptor (RXR) has been implicated in the regulation of multiple hormonal signaling pathways through the formation of heteromeric receptor complexes that bind DNA with high affinity. We now demonstrate that ultraspiracle (usp), a Drosophila RXR homolog, can substitute for RXR in stimulating the DNA binding of receptors for retinoic(More)
Mutations in the tumor suppressor gene PATCHED (PTC) are found in human patients with the basal cell nevus syndrome, a disease causing developmental defects and tumors, including basal cell carcinomas. Gene regulatory relationships defined in the fruit fly Drosophila suggest that overproduction of Sonic hedgehog (SHH), the ligand for PTC, will mimic loss of(More)
Identification of complementary DNAs encoding the human glucocorticoid receptor predicts two protein forms, of 777 (alpha) and 742 (beta) amino acids, which differ at their carboxy termini. The proteins contain a cysteine/lysine/arginine-rich region which may define the DNA-binding domain. Pure radiolabelled glucocorticoid receptor, synthesized in vitro, is(More)
The vitamin A derivative, retinoic acid, can regulate morphogenesis and differentiation in vertebrates. Two different subfamilies of the steroid receptor superfamily of transcription factors, the retinoic acid receptors and the retinoid X receptor, mediate the effects of retinoic acid. As part of an analysis of the hormonal control of development, we have(More)
TERT, the protein component of telomerase, serves to maintain telomere function through the de novo addition of telomere repeats to chromosome ends, and is reactivated in 90% of human cancers. In normal tissues, TERT is expressed in stem cells and in progenitor cells, but its role in these compartments is not fully understood. Here we show that conditional(More)
Basal cell carcinomas, the commonest human skin cancers, consistently have abnormalities of the hedgehog signaling pathway and often have PTCH gene mutations. We report here that Ptch+/- mice develop primordial follicular neoplasms resembling human trichoblastomas, and that exposure to ultraviolet radiation or ionizing radiation results in an increase in(More)
Molecular cloning has demonstrated that the receptors for steroid, retinoid and thyroid hormones are part of a large superfamily of nuclear regulatory proteins. In vertebrates these molecules regulate diverse biological processes such as pattern formation, cellular differentiation and homeostasis. The universal necessity for embryonic and adult cells to(More)
Nuclear hormone receptors comprise a superfamily of ligand-modulated transcription factors that mediate the transcriptional activities of steroids, retinoids, and thyroid hormones. A growing number of related proteins have been identified that possess the structural features of hormone receptors, but that lack known ligands. Known as orphan receptors, these(More)
The central part of the medial preoptic nucleus (MPNc), the encapsulated part of the bed nucleus of the stria terminalis (BSTe), and the posterodorsal part of the medial nucleus of the amygdala (MeAp) are all though to be involved in the neural control of female reproductive behavior, as well as other neuroendocrine mechanisms. Although the developmental(More)