High Expression of the DNA Methyltransferase Gene Characterizes Human Neoplastic Cells and Progression Stages of Colon Cancer

• Published in: Proceedings of the National Academy of Sciences - PNAS 1991-04, Vol.88 (8), p.3470-3474
• Main Authors: El-Deiry, Wafik S., Nelkin, Barry D., Celano, Paul, Yen, Ray-Whay Chiu, Falco, Joseph P., Hamilton, Stanley R., Baylin, Stephen B.
• Format: Article
• Language: English
• Subjects: 550201 - Biochemistry- Tracer Techniques; ANIMAL CELLS; ANIMALS; AZINES; Base Sequence; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; Blotting, Northern; BODY; Cancer; CARBON-GROUP TRANSFERASES; CARCINOGENESIS; Cell Division; Cell lines; chromosome 19; Chromosome Mapping; Chromosomes, Human, Pair 19; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Complementary DNA; DIGESTIVE SYSTEM; DNA; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA HYBRIDIZATION; ENZYMES; Gastroenterology. Liver. Pancreas. Abdomen; GASTROINTESTINAL TRACT; Gene Expression; GENE REGULATION; Genes; HETEROCYCLIC COMPOUNDS; Humans; HYBRIDIZATION; HYDROGEN COMPOUNDS; INTESTINES; MAMMALS; MAN; Medical sciences; METHYL TRANSFERASES; Methylation; Mice; Molecular Sequence Data; Mucosa; Neoplasia; Neoplasms - enzymology; NUCLEOSIDES; NUCLEOTIDES; Oligonucleotides - chemistry; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PATHOGENESIS; Polymerase Chain Reaction; PRIMATES; PROTEINS; PYRIMIDINES; RIBOSIDES; RNA; RNA, Messenger - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; THYMIDINE; TRANSFERASES; TRITIUM COMPOUNDS; TUMOR CELLS; Tumor Cells, Cultured; Tumors; VERTEBRATES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.8.3470

DNA methylation abnormalities occur consistently in human neoplasia including widespread hypomethylation and more recently recognized local increases in DNA methylation that hold potential for gene inactivation events. To study this imbalance further, we have cloned and localized to chromosome 19 a portion of the human DNA methyltransferase gene that codes for the enzyme catalyzing DNA methylation. Expression of this gene is low in normal human cells, significantly increased (30- to 50-fold by PCR analysis) in virally transformed cells, and strikingly elevated in human cancer cells (several hundredfold). In comparison to colon mucosa from patients without neoplasia, median levels of DNA methyltransferase transcripts are 15-fold increased in histologically normal mucosa from patients with cancers or the benign polyps that can precede cancers, 60-fold increased in the premalignant polyps, and >200-fold increased in the cancers. Thus, increases in DNA methyltransferase gene expression precede development of colonic neoplasia and continue during progression of colonic neoplasms. These increases may play a role in the genetic instability of cancer and mark early events in cell transformation.