Keratinocyte Transglutaminase Expression Varies in Squamous Cell Carcinomas

Duvic, Madeleine; Nelson, Deidra Chema; Annarella, Mary; Cho, Mimi; Esgleyes-Ribot, Teresa; Remenyik, Éva; Ulmer, Roseann; Rapini, Ronald P.; Sacks, Peter G.; Davies, Peter J.; Thacher, Scott M.

doi:10.1111/1523-1747.ep12373021

Cited by 27 publications

(14 citation statements)

References 48 publications

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“…In contrast, in SCC tumor cells, TG1 protein was expressed at cell membranes, while TG activity was seen in cytoplasm. In BCC, while TG1 protein was not expressed as shown in previous study (4), weak TG activity was observed.…”

Section: Discussionsupporting

confidence: 47%

Distinct protein expression and activity of transglutaminases found in different epidermal tumors

Karashima

Furumura

Ishii

et al. 2014

Experimental Dermatology

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We investigated protein expression and in situ activity of transglutaminases (TGs) in normal skin and various epidermal neoplasms. In normal skin, TG1 protein expression and TG activity were found at keratinocyte cell membranes in upper epidermis and granular layer, respectively. In seborrhoeic keratosis, TG1 protein was expressed evenly throughout tumors, while TG activity increased in gradient fashion from lower tumor area to cornified layer. In squamous cell carcinoma, TG1 protein was expressed at inner side of cell membranes, whereas TG activity was found in cytoplasm predominantly at horn pearls. In basal cell carcinoma, weak TG activity was found in cytoplasm of all tumor cells without the presence of TG1 protein.Immunoblotting and in situ activity assays using specific substrate peptides confirmed that TG2, but not TG1, contributed to the TG activity. These results suggested that different expression and activation of TGs may contribute to characteristics of the skin tumors.

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Section: Discussionsupporting

confidence: 47%

Distinct protein expression and activity of transglutaminases found in different epidermal tumors

Karashima

Furumura

Ishii

et al. 2014

Experimental Dermatology

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“…Keratinocytes are known to change greatly their gene expression during terminal cell differentiation. The expression of keratinocyte transglutaminase, which is an intracellular enzyme involved in cross-linking of intracellular proteins during terminal differentiation and cornification of skin cells, was shown to be regulated by DNA methylation (51). Therefore, it is likely to assume that ABO gene expression is also influenced by methylation of the promoter region through cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Expression of Human Histo-blood Group ABO Genes Is Dependent upon DNA Methylation of the Promoter Region

Kominato¹,

Hata²,

Takizawa³

et al. 1999

Journal of Biological Chemistry

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We have investigated the regulatory role of DNA methylation in the expression of the human histo-blood group ABO genes. The ABO gene promoter region contains a CpG island whose methylation status correlates well with gene expression in the cell lines tested. The CpG island was found hypomethylated in some cell lines that expressed ABO genes, whereas the other cell lines that did not express ABO genes were hypermethylated. The ABO blood group system discovered by Karl Landsteiner (1) at the beginning of this century is of great importance in blood transfusions and organ transplantations. Two carbohydrate antigens, A-and B-antigens, and their antibodies constitute this system. The A and B functional alleles at the ABO genetic locus encode glycosyltransferases ␣133GalNAc transferase (designated A-transferase) and ␣133Gal transferase (designated B-transferase), respectively. A-transferase transfers a GalNAc residue from UDP-GalNAc to the precursor H substrate, producing A antigens as defined by the trisaccharide determinant structure, GalNAc␣133(Fuc␣132)Gal␤13 R. Similarly, B-transferase catalyzes the transfer of a Gal from UDP-Gal to the same H substrate, producing B antigens defined by Gal␣133(Fuc␣132)Gal␤13 R (2-5). Molecular genetic studies of the human ABO genes have identified two critical single base substitutions that result in amino acid substitutions responsible for the different donor nucleotidesugar substrate specificity between A-and B-transferases. A single base deletion, which shifts the reading frame of codons and abolishes the function of A-transferase, has been identified in most O alleles (6, 7).The ABO genes are expressed in a cell type-specific manner; the isoantigens A, B, and H of blood groups A, B, and O are not confined to red cells only but are also found in most secretions and on some epithelial cells. However, they are absent in connective tissues and the central nervous system (8). ABH antigens are known to undergo drastic changes during development, differentiation, and maturation of normal cells (9). In addition to these physiological processes, profound changes have also been documented in pathological processes such as tumorigenesis. Reduction or complete deletion of A/B antigen expression in bladder and oral cancers has been documented, as well as the apparent onco-developmental expression of the ABH antigens in gastric and distal colon tumors (10 -12). Moreover, the loss of ABH antigens has been correlated with tumor progression of various carcinomas including lung and bladder carcinomas (13-16). Thus, delineation of regulatory mechanism is essential to understand these complicated expression patterns of the ABO genes.In an initial attempt to elucidate the molecular mechanism controlling the expression of the human ABO genes, we isolated several genomic clones that covered the ABO genes over 18 kb 1 (17). A 4.7-kb EcoRI/NcoI 5Ј-upstream fragment flanking the coding sequence in exon 1 of the human ABO gene was subcloned into the promoterless pGL3-basic vector upstream of the lucifer...

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“…body (B-C1) is used (25). In our hands and using our antiThis contrasts with the statistical significance observed on body, the cytosolic compartment and the cytoplasmic membrane of bronchial cells were labeled, similarly to previous comparison of NSCLC and SCLC (Table 1) studies on keratinocytes.…”

Section: Tgase 1 Expression In Lung Cancermentioning

confidence: 92%

In Vivo Transglutaminase Type 1 Expression in Normal Lung, Preinvasive Bronchial Lesions, and Lung Cancer

Martinet

Bonnard

Régnault

et al. 2003

Am J Respir Cell Mol Biol

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Transglutaminase type 1 (TGase 1) is a member of a class of enzymes that catalyze the cross-linking of proteins, a characteristic feature of epidermal differentiation and squamous metaplasia. The role of TGase 1 has been extensively studied in epidermis but not in the lung. Using a polyclonal anti-TGase 1 antibody prepared in our laboratory (TGase-lac), TGase 1 expression in normal bronchial epithelium, bronchial preinvasive lesions, and lung cancer was characterized. The specificity of the antibody was confirmed by the presence in squamous differentiated bronchial cells of specific 106-kD and 92-kD bands by Western blotting. In addition, immunohistochemistry displayed a recognized pattern of labeling in both normal and tumor cells beneath the cytoplasmic membrane and within the cytosol. TGase 1 was shown to be expressed by cells from bronchial epithelium and bronchial preinvasive lesions, strongly expressed in most non-small-cell lung cancer tumor cells and in apoptotic bodies, but weakly expressed in small-cell lung cancer. The distribution of TGase 1 mRNA correlated with the immunohistochemical profile. These observations suggest that TGase 1 expression is a normal feature of bronchial epithelium and is linked to the process of squamous differentiation occurring in preinvasive lesions. Its role in lung cancer remains to be clarified.

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Keratinocyte Transglutaminase Expression Varies in Squamous Cell Carcinomas

Cited by 27 publications

References 48 publications

Distinct protein expression and activity of transglutaminases found in different epidermal tumors

Distinct protein expression and activity of transglutaminases found in different epidermal tumors

Expression of Human Histo-blood Group ABO Genes Is Dependent upon DNA Methylation of the Promoter Region

In Vivo Transglutaminase Type 1 Expression in Normal Lung, Preinvasive Bronchial Lesions, and Lung Cancer

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