Premium
Regulation of the differentiation‐related gene Drg‐1 during mouse skin carcinogenesis
Author(s) -
GómezCasero Elena,
Navarro Manuel,
RodríguezPuebla Marcelo L.,
Larcher Fernando,
Paramio Jesús M.,
Conti Claudio J.,
Jorcano José L.
Publication year - 2001
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.1069
Subject(s) - carcinogenesis , keratinocyte , biology , cellular differentiation , gene expression , gene , downregulation and upregulation , cell culture , microbiology and biotechnology , regulation of gene expression , cancer research , genetics
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 G 0 , which increased in early G 1 and decreased afterwards in late G 1 /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.