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- W2740399140 abstract "Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk. Address for correspondence: schly@mail.ru. E. V. Gorshkova Predisposition of inbred mice to lung cancer is determined by three genetic loci, named Pas (pulmonary adenoma susceptibility) [9]. Pas1 locus on chromosome 6 includes K-ras gene [5,10]. Study of K-ras gene revealed a correlation between susceptibility of inbred mice (M. musculus) to pulmonary adenomas and single nucleotide polymorphism (SNP) in positions 288 and 296 n. p. in the beginning of intron 2 [2,4]. Susceptible mice have nucleotides C and A in these positions, respectively, while resistant mice have G and C nucleotides. We previously showed that “susceptible” CA variant of K-ras gene intron 2 SNP corresponds to GATA-6 transcription factor binding site, while in the “resistant” GC variant this site is destroyed [1]. Since GATA-6 is the key factor of lung tissue differentiation and regulation of gene expression in the lungs [8,11], we hypothesized that differences in the binding of this factor to different allele states of K-ras gene intron 2 are essential for the formation of lung tumorigenesis-sensitive or resistant phenotype [1]. However, detection of sensitive CA variant of K-ras gene intron 2 SNP in M. spretus resistant to lung tumorigenesis [10] raised doubt about participation of this polymorphism in the predisposition to carcinogenesis in the lungs. On the other hand, M. spretus have one more mononucleotide substitution C (M. musculus)→T (M. spretus) in position 311 n. p. in the immediate vicinity of SNP in positions 288 and 296 n. p. responsible for the appearance or disappearance of GATA-6 binding site. We therefore hypothesized that this substitution could modify binding site for some transcription factor capable of forming a composition regulatory element together with GATA-6 binding site and be associated with the resistance to lung cancer in M. spretus. This study was aimed at verification of this hypothesis." @default.
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- W2740399140 date "2006-01-01" @default.
- W2740399140 modified "2023-09-26" @default.
- W2740399140 title "Lung Cancer-Associated SNP at the Beginning for Transcription Factor Binding" @default.
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