A Novel Aspartic Proteinase-Like Gene Expressed in Stratified Epithelia and Squamous Cell Carcinoma of the Skin

Abstract

Homeostasis of stratified epithelia, such as the epidermis of the skin, is a sophisticated process that represents a tightly controlled balance between proliferation and differentiation. Alterations of this balance are associated with common human diseases including cancer. Here, we report the cloning of a novel cDNA sequence, from mouse back skin, that is induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and codes for a hitherto unknown aspartic proteinase-like protein (Taps). Taps represents a potential AP-1 target gene because TPA-induced expression in epidermal keratinocytes critically depends on c-Fos, and co-treatment with dexamethasone, a potent inhibitor of AP-1-mediated gene regulation, resulted in impaired activation of Taps expression. Taps mRNA and protein are restricted to stratified epithelia in mouse embryos and adult tissues, implicating a crucial role for this aspartic proteinase-like gene in differentiation and homeostasis of multilayered epithelia. During chemically induced carcinogenesis, transient elevation of Taps mRNA and protein levels was detected in benign skin tumors. However, its expression is negatively associated with dedifferentiation and malignant progression in squamous cell carcinomas of the skin. Similar expression was observed in squamous skin tumors of patients, suggesting that detection of Taps levels represents a novel strategy to discriminate the progression state of squamous skin cancers.

Internal environment in cancer patients and proposal that carcinogenesis is adaptive response of glycolysis to overcome adverse internal conditions

“…Although many investigators have considered that carcinogens such as ultraviolet rays, food additives, air pollution, etc. [8][9][10][11][12], induce multiple mutation steps in proto-oncogenes, there is an alternative possibility that such mutation is a process of glycolytic adaptation by living beings, namely, cancer cells. Hypothermia, hypoxia and hyperglycemia, which are induced by continuous stress (due to the lifestyle in patients), might be important factors which induce the adaptive response.…”

Kallikrein 6 Induces E-Cadherin Shedding and Promotes Cell Proliferation, Migration, and Invasion

“…3,4). Recently, we applied global gene expression analysis on samples derived from distinct tumor stages and could identify a comprehensive list of novel tumor-associated genes (5)(6)(7)(8)(9)(10). One of the differentially expressed genes showing enhanced expression in advanced tumor stages encodes the brain and skin serine proteinase Bssp [also known as kallikrein 6 (Klk6) according to the recommendation for future nomenclature of kallikrein-related peptidases (11)].…”

Endogenous Retroviral-Like Aspartic Protease, SASPase as a Key Modulator of Skin Moisturization

“…Although there are putative transmembrane domains in human and mouse SASPase, the full-length protein was not detected in epidermal lysates of human and mouse. It has also been demonstrated that mouse SASPase is found in the medium when the full-length protein was expressed in the HeLa cell line [ 60 ] . Thus, the function of the transmembrane domain of SASPase remains to be elucidated.…”

“…Using high-throughput in situ hybridization screening, we have also identifi ed a mouse homolog of SASPase [ 35 ] as an SG-expressing gene. This protease has also been cloned as a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced gene (Taps) from cDNA of mouse back skin epidermis [ 60 ] . Human and mouse SASPase/Asprv1/Taps were primarily expressed in skin and exclusively expressed in the SG of the epidermis ( Fig.…”