Evidence that the familial adenomatous polyposis gene is involved in a subset of colon cancers with a complementable defect in c-myc regulation

Journal Article · Thu Jun 01 00:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.11.4264· OSTI ID:5159972

Erisman, M D; Scott, J K; Astrin, S M ^[1]

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1. Fox Chase Cancer Center, Philadelphia, PA (USA)

Human colorectal carcinomas frequently express elevated levels of c-myc mRNA in the absence of a gross genetic change at the c-myc locus. To test the hypothesis that these tumors are defective in a gene function necessary for the regulation of c-myc expression, the authors fused an osteosarcoma cell line that exhibits normal c-myc regulation with two colon carcinoma cell lines that express deregulated levels of c-myc mRNA. Since rates of c-myc mRNA turnover in the colon carcinoma cells were found to be comparable to those in normal cells, increased message stability cannot account for the increased steady-state levels of transcripts. These finding suggest that loss of function of a trans-acting regulator is responsible for the deregulation of c-myc expression in a major fraction of colorectal carcinomas. Analysis of restriction fragment length polymorphisms in tumor/normal tissue pairs from patients with primary colorectal lesions indicated that deregulation of c-myc expression in the tumors is correlated with frequent loss of alleles of syntenic markers on chromosome 5q. Chromosome 5q is the region known to contain the gene for familial adenomatous polyposis, an inherited predisposition to colon cancer. These findings, together with the arlier finding that the colonic distribution of tumors exhibiting deregulated c-myc expression is similar to that reported for familial polyposis, provide evidence that loss of function of the familial adenomatous polyposis gene is involved in a subset of colorectal cancers in which c-myc expression is deregulated.

• OSTI ID: 5159972
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:11; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARCINOGENESIS
MOLECULAR BIOLOGY
MESSENGER-RNA
AUTORADIOGRAPHY
TUMOR CELLS
GENE REGULATION
CARCINOMAS
DNA
DNA HYBRIDIZATION
ETIOLOGY
GENES
HYBRIDIZATION
LARGE INTESTINE
MAN
OSTEOSARCOMAS
PHOSPHORUS 32
RECTUM
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
GASTROINTESTINAL TRACT
INTESTINES
ISOTOPES
LIGHT NUCLEI
MAMMALS
NEOPLASMS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
RNA
SARCOMAS
SKELETAL DISEASES
VERTEBRATES
550401* - Genetics- Tracer Techniques