Serum-responsive expression of carbonyl-metabolizing enzymes in normal and transformed human buccal keratinocytes

Abstract

Gene expression of carbonyl-metabolizing enzymes (CMEs) was investigated in normal buccal keratinocytes (NBK) and the transformed buccal keratinocyte lines SVpgC2a and SqCC/Y1. Studies were performed at a serum concentration known to induce terminal squamous differentiation (TSD) in normal cells. Overall, 39 of 58 evaluated CMEs were found to be expressed at the transcript level. Together the transformed cell lines showed altered transcription of eight CME genes compared to NBK, substantiating earlier results. Serum increased transcript levels of ALDH1A3, DHRS3, HPGD and AKR1A1, and decreased those of ALDH4A1 in NBK; of these, the transformed, TSD-deficient cell lines partly retained regulation of ALDH1A3 and DHRS3. Activity measurements in crude cell lysates, including relevant enzymatic inhibitors, indicated significant capacity for CME-mediated xenobiotic metabolism among the cell lines, notably with an increase in serum-differentiated NBK. The results constitute the first evidence for differential CME gene expression and activity in non-differentiated and differentiated states of epithelial cells.

p53-inducible DHRS3 Is an Endoplasmic Reticulum Protein Associated with Lipid Droplet Accumulation

“…DHRS3 expression was shown to be up-regulated in transformed buccal keratinocytes (38), papillary thyroid carcinomas (39,40), and neuroblastomas (41). The up-regulated expression may limit the activity of RA, which is generally thought to have an inhibitory effect on the cell cycle and promote apoptosis in some cancer cell lines (6), thereby exerting a prosurvival effect.…”

DHRS3, a retinal reductase, is differentially regulated by retinoic acid and lipopolysaccharide-induced inflammation in THP-1 cells and rat liver

“…The DHRS3 gene maps to a region of human chromosome 1 at band p36.1 (15), which is frequently lost in aggressive neuroblastoma tumors (3). DHRS3 expression was reported to be induced by retinoids in neuroblastoma cell lines (3) and in naïve CD4 ϩ T cells (19) and by the retinoid X receptor (RXR) rexinoid ligand bexarotene in MMTV-erbB2 mice (23) and to be responsive to serum concentration in normal and transformed human buccal keratinocytes (39). Recent studies have shown that DHRS3 is regulated by p53 and p63 tumor suppressor proteins (20) and is able to promote lipid droplet storage in HepG2 cells, consistent with the localization of DHRS3 in the endoplasmic reticulum (8).…”