Molecular Biology of the Vitamin D Hormone

Analysis of the vitamin D system in basal cell carcinomas (BCCs)

“…3 Vitamin D response elements are beginning to be identified in genes involved in cellular growth, differentiation, apoptosis, invasion and metastasis of tumor cells; that is, cell cycle regulators such as the human p21/WAF1, cyclin A and cyclin E genes, the human nm23.H1 gene, the human c-fms, c-fos, c-jun, and c-myc genes, the human retinoblastoma gene, the murine fibronectin gene, the human plasminogen activator inhibitor 2 gene, the human laminin and laminin receptor (a6) genes, and the chicken b3-integrin gene. 7,43,44 Therefore, we conclude that modulation of VDR expression may be of importance for the unique growth characteristics of BCCs.…”

“…8,45,46 Different classes of vitamin D response elements have been identified that are activated either by VDR-homodimers or by heterodimers of VDR and RXRs or retinoic acid receptors (RAR). 7 It was demonstrated that ligands for RXRs and RARs can enhance the transcriptional activity of 1,25-D 3 mediated nuclear signaling pathways. 7 We have shown expression of RXR and RAR-isotypes in BCCs previously.…”

“…7 It was demonstrated that ligands for RXRs and RARs can enhance the transcriptional activity of 1,25-D 3 mediated nuclear signaling pathways. 7 We have shown expression of RXR and RAR-isotypes in BCCs previously. 47 Therefore, we conclude that different vitamin D signaling pathways are present in BCCs that are determined by the RXR-or RARligand and the nature of the response element.…”

“…4,5 VDR belongs to the superfamily of trans-acting transcriptional regulatory factors, which includes the steroid and thyroid hormone receptors as well as the retinoid-X receptors and retinoic acid receptors. [6][7][8] Keratinocytes express VDR, 1,9 whose natural ligand, calcitriol, inhibits proliferation and induces differentiation of cultured human keratinocytes in vitro. 1,3 Transcriptional regulation of cell cycle regulatory proteins including WAF-1, and other proteins involved in keratinocyte growth and differentiation, including b 3 -integrin and fibronectin, by calcitriol has been shown.…”

Endogenous retinoid X receptors can function as hormone receptors in pituitary cells.

“…In each case, target gene binding by the nuclear hormone receptor is greatly enhanced by its partnership with RXR. It is clear that RXR functions as an unliganded partner for TR and VDR in gene regulation by thyroid hormone (T3) and vitamin D, as these hormones have biological effects in the absence of added retinoids (5,21,29,35,41,49,54,62). Retinoid binding by RXR may further modulate the transcriptional response to T3 and vitamin D in some cases (13,39,51,65).…”