Positive selection of candidate tumor-suppressor genes by subtractive hybridization

Journal Article · Mon Apr 01 00:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.7.2825· OSTI ID:5026573

Lee, S W; Tomasetto, C; Sager, R ^[1]

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1. Dana-Farber Cancer Inst., Boston, MA (United States)

A positive selection system designed to identify and recover candidate tumor-suppressor genes is described. The system compares mRNA expression of genes from normal and tumor-derived human mammary epithelial cells grown in a special medium that supports similar growth rates of the two cell types. mRNAs uniquely expressed in normal cells are recovered as cDNAs after subtraction with mRNA from tumor cells. Seven different clones, from 0.6 to 4.8 kilobases in transcript size and including both rare and abundant transcripts, were recovered in the first 23 clones analyzed. Among the isolated clones were genes encoding the gap-junction protein connexin 26, two different keratins, and glutathione-S-transferase {pi}, as well as an unknown gene in the S100 family of small calcium-binding proteins. In principle, tumor-suppressor genes include two classes: class I, in which loss of function results from mutation or deletion of DNA and class II, in which loss of function is from a regulatory block to expression. A class II suppressor gene is assumed to be regulated by a different suppressor gene that lost its function by mutation or deletion. Both classes of tumor-suppressor genes may provide valuable proteins with clinical applications in cancer diagnosis or therapy. Class II suppressors may be especially useful because the normal genes are present and their reexpression may be inducible by drugs or other treatments.

• OSTI ID: 5026573
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:7; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENES
DNA HYBRIDIZATION
NEOPLASMS
GENE REGULATION
ELECTROPHORESIS
EPITHELIUM
GENE REPRESSORS
GLUTATHIONE
MAMMARY GLANDS
MESSENGER-RNA
PHOSPHORUS 32
PROTEINS
RECOMBINANT DNA
TRANSFERASES
WOMEN
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
DRUGS
ENZYMES
FEMALES
GLANDS
HYBRIDIZATION
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
NUCLEI
NUCLEIC ACIDS
NUCLEOPROTEINS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PHOSPHORUS ISOTOPES
POLYPEPTIDES
PRIMATES
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RNA
TISSUES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques