Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms

Abstract

STEAP1 gene is overexpressed in several kinds of tumors, particularly in prostate cancer. Besides STEAP1, there is another related gene, STEAP1B, which may encode two different transcripts. Although several studies have been pointing STEAP1 as a putative immunotherapeutic target and biomarker, the mechanisms underlying its regulation are not fully understood. In silico analysis allowed us to show that STEAP1 and STEAP1B share high homology, but with slight differences at structural level. Experiments with prostate cells showed that STEAP1B2 is overexpressed in cancer cells. Regarding STEAP1 regulation, it is demonstrated that the stability of mRNA and protein is higher in LNCaP than in PNT1A cells. Of note, serum triggered opposite effects in LNCaP and PNT1A in relation to STEAP1 stability, e.g., increasing it in PNT1A and decreasing in LNCaP. These results suggest that STEAP1 may be regulated by post-transcriptional and post-translational modifications (PTM), which may differ between non-neoplastic and neoplastic cells. These PTM are supported through in silico analysis, where several modifications such as N-glycosylation, N-Glycation, Phosphorylation and O-linked β-N-acetylglucosamine, may occur in STEAP1 protein. In conclusion, these data indicate that STEAP1B2 is overexpressed in neoplastic cells, and PTM may be involved in regulation of STEAP1 expression in prostate cells.

Novel potent anti-STEAP1 bispecific antibody to redirect T cells for cancer immunotherapy

“…A BLASTp search ( https://blast.ncbi.nlm.nih.gov/ ) confirmed the presence of this second ECD sequence on STEAP1B, encoded by a gene on human chromosome 7p (in contrast to STEAP1 on 7q). The epitope on the second ECD was also previously reported in two other isoforms, STEAP1B1 and STEAP1B2 in humans 47 as well as STEAP1 in cynomolgus monkey.…”

Tailoring heated intraperitoneal mitomycin C for peritoneal metastases originating from colorectal carcinoma: a translational approach to improve survival

“…The discrepancies between mRNA and IHC that we found in two cell lines could be because of post-translational modifications. This complex process, consisting of several interacting proteins, is known to mediate protein expression and often relays mRNA expression in different levels of protein expression ( Gomes et al , 2014 ).…”

Regulatory Roles of Six-Transmembrane Epithelial Antigen of the Prostate Family Members in the Occurrence and Development of Malignant Tumors

“…Non-neoplastic prostate cells show little to no STEAP1B1 and STEAP1B2 mRNA expression. On the other hand, in malignant prostate cells, LNCaP and PC3, STEAP1B2 is highly expressed, whereas STEAP1B1 mRNA is mainly expressed on PNT2 and PC3 cells, and under-expressed on LNCaP cells (Gomes et al, 2014b).…”

“…The structure of STEAP1B is different from other proteins. STEAP1B has only four potential transmembrane regions and intracellular COOH and NH2 terminal regions (Gomes et al, 2014b). Without an NADPH oxidoreductase domain and a hemebinding site, STEAP1B is predicted to lack oxidoreductase activity (Grunewald et al, 2012a).…”

“…The six-transmembrane epithelial antigen of the prostate (STEAP) family proteins belong to a class of cellular transmembrane proteins. With five members so far, namely STEAP1-4 and STEAP1B, STEAP proteins possess a similar structure comprised of 4-6 transmembrane domains and intracellular amino-and carboxyl-terminal domains (Hubert et al, 1999;Rinaldy and Steiner, 1999;Zhang et al, 2001;Korkmaz et al, 2002Korkmaz et al, , 2005Grunewald et al, 2012a;Gomes et al, 2014b). Except for the highly homologous STEAP1 and STEAP1B, all other members have general metal reductase activity catalyzed by an F420H2:NADP+ oxidoreductase (FNO)-like domain (Knutson, 2007).…”