Down-regulation of epidermal growth factor receptor by selective expansion of a 5'-end regulatory dinucleotide repeat in colon cancer with microsatellite instability.

Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in several tumor types, and its expression is influenced by the length of a 5'-end microsatellite repeat (CA)n: the longer the repeat, the lower the expression. Dinucleotide repeats accumulate insertion/deletion types of mutations in tumors with microsatellite instability. We designed this study to estimate the occurrence of these mutations in EGFR(CA)n and their relevance in carcinogenesis of microsatellite instability-positive colon and gastric tumors.

Topoisomerase II gene mutations in tumors and tumor cell lines with microsatellite instability.

Genetic or epigenetic inactivation of the DNA mismatch repair genes in tumor precursor cells results in a strong mutator phenotype, known as the microsatellite mutator phenotype (MMP), or microsatellite instability (MSI). This mutator phenotype causes mutations in genes responsible for the regulation of cell growth and survival/death and thus promotes the development and progression of tumors. In the present study, we examined the DNA topoisomerase II genes (topIIalpha and topIIbeta) as mutational targets for MMP.

Hypersensitivity of tumor cell lines with microsatellite instability to DNA double strand break producing chemotherapeutic agent bleomycin.

Genetic or epigenetic inactivation of DNA mismatch repair genes results in a strong mutator phenotype, known as the microsatellite mutator phenotype or microsatellite instability (MSI). This mutator phenotype causes mutations in genes responsible for the regulation of cell growth and survival/death and thus promotes the development and progression of tumors. In addition to such tumorigenic lesions, mutations in genes of other types of DNA repair, for example, DNA double-strand break (DNA DSB) repair, are found in tumor cells with MSI.

The matrix metalloproteinase-21 gene 572C/T polymorphism and the risk of breast cancer.

Background: Matrix metalloproteinases (MMPs) contribute in multiple ways to all stages of tumor development, and a number of DNA polymorphisms in the MMP genes are associated with an increased risk of cancer. We previously identified the MMP-21 gene 572C/T polymorphism leading to Ala191Val substitution within the enzyme's catalytic domain. We performed a case-control study to test association between this polymorphism and the risk of breast cancer.