KMID : 0620920090410010042
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Experimental & Molecular Medicine 2009 Volume.41 No. 1 p.42 ~ p.50
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Expression of N-terminal truncated desmoglein 3 (¥ÄNDg3) in epidermis and its role in keratinocyte differentiation
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Lee Jung-Suk
Yoon Hyun-Kyung Sohn Kyung-Cheol Back Seung-Ju Kee Sun-Ho Seo Young-Joon Park Jang-Kyu Kim Chang-Duk Lee Jeung-Hoon
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Abstract
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During a search for keratinocyte differentiation-related genes, we obtained a cDNA fragment from the 5¡¯-untranslated region of a previously identified splicing variant of desmoglein 3 (Dg3). This transcript encodes a protein of 282 amino acids, which corresponds to the N-terminal truncated intracellular domain of Dg3 (¥ÄNDg3). Northern blot analysis detected a 4.6-kb transcript matching the predicted size of ¥ÄNDg3 mRNA, and Western blot analysis with an antibody raised against the Dg3 C-terminus (H-145) detected a 31-kDa protein. Increased ¥ÄNDg3 expression was observed in differentiating keratinocytes by RT-PCR and Western blot analysis, suggesting that ¥ÄNDg3 is indeed a differentiation- related gene product. In immunohistochemical studies of normal and pathologic tissues, H-145 antibody detected the protein in the cytoplasm of suprabasal layer cells, whereas an antibody directed against the N-terminal region of Dg3 (AF1720) reacted with a membrane protein in the basal layer. In addition, ¥ÄNDg3 transcript and protein were upregulated in psoriatic epidermis, and protein expression appeared to increase in epidermal tumors including Bowen¡¯s disease and squamous cell carcinoma. Moreover, overexpression of ¥ÄNDg3 led to increased migration and weakening of cell adhesion. These results suggest that ¥ÄNDg3 have a role in keratinocyte differentiation, and that may be related with tumorigenesis of epithelial origin.
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KEYWORD
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cell adhesion, cell differentiation, cell movement, desmoglein 3, epidermis, keratinocytes, skin neoplasms
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