Detection and cloning of epidermal zinc‐α ₂ ‐glycoprotein cDNA and expression in normal human skin and in tumors

Abstract

Zinc-alpha 2-glycoprotein (Zn alpha 2gp) is almost ubiquitous in body fluids, and its antibody labels the corresponding secretory epithelia. We have found that Zn alpha 2gp is also expressed in human epidermis. We cloned the Zn alpha 2gp cDNA by screening our cDNA library, derived from epidermal keratinocytes, with a probe for prostate Zn alpha 2gp. It had complete nucleic acid sequence homology with that from prostate, including the signal peptide. Just as Zn alpha 2gp expression is higher in more differentiated breast tumors, so in skin tumors the highest mRNA levels occurred in the normal controls, the lowest in basal cell carcinomas (the least differentiated epidermal tumor type), and intermediate levels in squamous cell carcinomas and Merkel cell carcinomas. A similar increase in Zn alpha 2gp gene expression with differentiation was observed when epidermal keratinocytes were cultured in media that varied in cellular maturation potential.

Reduction of AZGP1 predicts poor prognosis in esophageal squamous cell carcinoma patients in Northern China

“…Recently, AZGP1 has been highlighted to play a crucial role in carcinogenesis in human cancers 12–15. To our knowledge, this is the first study to explore the relationship between AZGP1 gene expression and human ESCC occurrence and development.…”

“…It was indicated that AZGP1 downregulation was associated with tumor cells poor differentiation in a majority of popular tumors, such as breast cancer, prostate cancer, oral squamous cell carcinomas, pancreatic cancer, cervical cancer, and gastric cancer 14,15,21–24. Because of its high structural homology to the major histocompatibility complex class I family, AZGP1 plays a antitumor role by participating the immune response 12.…”

Zinc α2-Glycoprotein: A Multidisciplinary Protein

“…The exon 4 also contains the entire 3 ¶-untranslated region, including a hexanucleotide AATAAA that probably represents the polyadenylation signal of the gene (32). The serum ZAG shows complete nucleotide sequence homology with that from the prostate, which includes the signal peptide (29). The full gene of ZAG was reported by Freije et al (8).…”

“…The concentration of ZAG has been reported to increase dramatically in carcinomas (3). Therefore, it is also considered as a good biomarker for prostate (27), breast (28), oral (22), and epidermal (29) carcinomas.…”

“…As previously reported, tumor necrosis factor-a also inhibits melanin synthesis by human primary melanoma and B16 melanoma cells (137,138), but ZAG inhibits melanin synthesis by B16 cells via a tumor necrosis factor -independent mechanism. ZAG is produced by normal epidermal keratinocytes, where its expression increases with cellular differentiation (29). It is also shown that keratinocyte-derived factors influence melanocyte behavior, including melanocyte proliferation, dendricity, and total melanin production (139,140).…”