Regulation of the differentiation-related gene Drg-1 during mouse skin carcinogenesis

• Published in: Molecular carcinogenesis Vol. 32; no. 2; pp. 100 - 109
• Main Authors: Gómez-Casero, Elena, Navarro, Manuel, Rodríguez-Puebla, Marcelo L., Larcher, Fernando, Paramio, Jesús M., Conti, Claudio J., Jorcano, José L.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.10.2001
• Subjects: 12-O-tetradecanoylphorbol-13-acetate; Animals; Carcinogens - toxicity; Cell Cycle Proteins - genetics; Cell Differentiation - genetics; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - genetics; Drg-1 gene; Genes, ras; H-ras gene; Intracellular Signaling Peptides and Proteins; keratinocyte differentiation; Keratinocytes - pathology; Mice; Mice, Inbred C57BL; Papilloma - chemically induced; Papilloma - genetics; Papilloma - pathology; ras; RNA, Messenger - genetics; Skin Neoplasms - chemically induced; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Tetradecanoylphorbol Acetate - toxicity
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.1069

Differentiation‐related gene‐1 (Drg‐1) has been identified as a gene whose expression is increased in several processes related to differentiation, but its function is currently unknown. In this report, we show that Drg‐1 was expressed in keratinocytes, this expression being rapidly increased as a result of induction by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) or the presence of an activating form of Ha‐ras. Induction by TPA occurred both in cultured cell lines and primary keratinocytes as well as in mouse skin after a single TPA application. Overexpression of Drg‐1 was also observed in TPA‐induced hyperplastic skin. In agreement, mouse skin papillomas and carcinomas also overexpressed Drg‐1. In addition, Drg‐1 was induced when keratinocytes were forced to differentiate by calcium switch or serum starvation. Analysis of the expression of Drg‐1 during the keratinocyte cell cycle demonstrated relatively high levels of Drg‐1 mRNA in G0, which increased in early G1 and decreased afterwards in late G1/S. In situ analysis showed an accumulation of Drg‐1 in the suprabasal layers of the skin, as well as in the more differentiated areas of mouse skin papillomas. These results suggest that, in addition to being upregulated during keratinocyte differentiation, the Drg‐1 gene might have a complex function in skin tumorigenesis. © 2001 Wiley‐Liss, Inc.