We have previously reported that the
heterogeneous nuclear ribonucleoprotein A1 (
hnRNP A1), a major
hnRNP, binds to G-rich repetitive sequences and quadruplex (G4') structures in
DNA, including the 5'-TTAGGG-3' telomere repeat and 5'-GGCAG-3' short-tandem-repeat.
DNA synthesis arrest at the (GGG) sites within these repeats in vitro was retrieved by the addition of the
hnRNP A1 protein or its N-terminal proteolytic product, UP1, in a dose-dependent manner. Therefore, functional perturbation of
hnRNP A1 may abrogate the
genomic stability of telomere repeats and other G-rich sequences, independent of its major role in transcriptional and translational regulation. In the present study, we conducted genetic and expression analysis of the
hnRNP A1 gene in sporadic human
colorectal cancers to clarify its possible involvement in human
carcinogenesis. Of 30 lesions, one harbored a mutation at the -11 position from the translation initiation site, but none in the coding region. A single nucleotide polymorphism, an A or G-allele, was found in the 5' upstream promoter region of the gene. Quantitative gene expression analysis revealed that 60% (18/30) of cases showed over-expression of
hnRNP A1 in
cancer tissues by 2-fold or greater, compared to their normal colon tissues, with values of 78, 64 and 40% for clinicopathological stages II, III and IV, respectively. Although the
biological consequences of
hnRNP A1 overexpression in
colorectal cancers remain to be clarified, it could contribute to maintenance of telomere repeats in
cancer cells with enhanced cell proliferation. Alternatively, since the variations in the stoichiometry of
hnRNP family
proteins are considered to affect cell-specific gene expression, quantitative alteration of
hnRNP A1 could result in facilitation of transformation of colon epithelial cells as a consequence of transcriptional and translational perturbation.