The 15kDa Selenoprotein Expression May Be Regulated Through The AhR Pathway

Several selenoproteins, including the 15kDa selenoprotein (Sep15), are thought to have roles in both cancer prevention and promotion. However, little is known about factors regulating Sep15 expression. Our preliminary analyses indicated that some dietary polyphenols, but not the NRF2-regulating isothiocyanate sulforaphane, decreased Sep15 mRNA expression in human colon cancer HT29 cells. Because many flavonoids are known to affect Arylhydrocarbon Receptor (AhR) and/or Nrf2-regulatory pathways, expression of AhR and Nrf2 related genes are being investigated in Sep15-deficient and -sufficient HT29 colon cancer cells to elucidate the potential regulatory mechanisms of Sep15. Comparison of the NCI-60 cell lines through CellMiner analysis revealed that mRNA expression of Sep15 and AhR were negatively correlated (p<0.05). Microarray analysis showed that mRNA expression of AhR-pathway-related genes were significantly changed in HT29 cells lacking Sep15 compared to controls, including the AhR-nuclear transporter, the AhR-interacting protein, and heat-shock protein 90. Furthermore, mRNA expression of TCCD-induced CYP1A1 and CYP1B1 was significantly lower in Sep15-deficient cells. Thus, Sep15 may influence or be regulated by AhR-dependent pathways, which may be important in regulation of colon carcinogenesis. Funding: National Cancer Institute Intramural support; Towson University Jess & Mildred Fisher Endowed Chair and a Faculty Development & Research Committee grant (PAT).