Codon 12 Region of Mouse K-ras Gene Is the Site for in vitro Binding of Transcription Factors GATA-6 and NF-Y

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E. V. Gorshkova^*, V. I. Kaledin, V. F. Kobzev, and T. I. Merkulova

Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, pr. Lavrentieva 10, 630090 Novosibirsk, Russia; fax: (3832) 33-1278; E-mail: schly@mail.ru

^* To whom correspondence should be addressed.

Received April 18, 2005; Revision received June 16, 2005

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Codon 12 of the K-ras gene is a generally recognized example of a mutational hot spot. By the approach of gel retardation and specific antibodies, a double-stranded oligonucleotide corresponding to the codon 12 region of the mouse K-ras gene (from 20 to 50 bp with respect to the exon 1 start) was found to be a site for cooperative binding of the transcription factors GATA-6 and NF-Y. GATA-6 and NF-Y were selectively activated with lung carcinogens 3-methylcholanthrene and nitrosoethylurea in mice of strains susceptible to lung tumorigenesis but not in animals of resistant strains. The interaction of GATA-6 and NF-Y with the codon 12 region of the K-ras gene is suggested to be involved in the mechanism of lung carcinogenesis.

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KEY WORDS: K-ras gene, codon 12, transcription factors GATA-6 and NF-Y, lung carcinogenesis

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