Anti-GPX2 (aa 126-190) polyclonal antibody

Cutaneous squamous cell carcinomas (CSCC) are a common malignancy of keratinocytes that arise in sites of the skin exposed to excessive UV radiation. In the present study, we show that human SCC cell lines, preneoplastic solar keratoses (SK), and CSCC are associated with perturbations in glutathione peroxidase (GPX) activity and peroxide levels. Specifically, we found that two of three SKs and four of five CSCCs, in vivo, were associated with decreased GPX activity and all SKs and CSCCs were associated with an elevated peroxide burden. Given the association of decreased GPX activity with CSCC, we examined the basis for the GPX deficiency in the CSCCs. Our data indicated that GPX was inactivated by a post-translational mechanism and that GPX could be inactivated by increases in intracellular peroxide levels. We next tested whether the decreased peroxidase activity coupled with an elevated peroxidative burden might contribute to CSCC formation in vivo. This was tested in Gpx1(-/-) and Gpx2(-/-) mice exposed to solar-simulated UV radiation. These studies showed that Gpx2 deficiency predisposed mice to UV-induced CSCC formation. These results suggest that inactivation of GPX2 in human skin may he an early event in UV-induced SCC formation.

NKX3.1 is a prostate-specific transcription factor that is regulated by the androgen receptor in the presence of androgens. It functions as a tumor suppressor against the development of prostatic intraepithelial neoplasia and primary prostate tumors. Here, a recognized approach combining in silico analysis and chromatin immunoprecipitation (ChIP) was used to identify the genes directly regulated by NKX3.1 promoter binding in LNCaP cells. Quantitative PCR using ChIP-captured DNAs as templates verified a subset of NKX3.1 binding motifs. Thus, in the presence of androgens, significant NKX3.1 binding occurs to promoters of GPX2, QSCN6, SOD1, and SOD2 genes that contribute to oxidative stress regulation. Our data demonstrate that NKX3.1 is found in a DNA-bound state transiently at a basal level even in the absence of androgens; an increase in androgens promotes NKX3.1 binding, perhaps temporally rather than spatially, to the specific sites. The overall changes potentiate the transcriptional regulatory activity of NKX3.1, although they are dependent on the androgen receptor for the target promoters. The results suggest that NKX3.1 contributes to an antioxidant response by regulating the transcription of oxidative stress regulators by direct promoter binding.