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Suppression of deregulated c-MYC expression in human colon carcinoma cells by chromosome 5 transfer

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (United States)
;  [1];  [2]
  1. Fox Chase Cancer Center, Philadelphia, PA (United States)
  2. Univ. of California, Irvine (United States)

Two-thirds of sporadic colon carcinomas express elevated levels of the c-MYC protooncogene. In addition, most colon carcinoma cell lines show constitutive elevated expression (10- to 40-fold over normal) of MYC RNA and protein that is not modulated in response to a mitogenic stimulus. Indirect immunofluorescence has been used to detect c-MYC protein in such cell lines, in hybrid cells resulting from fusions of such lines with cells that regulate MYC normally, and in carcinoma cells to which a normal copy of chromosome 5 has been transferred by microcell fusion. The deregulated expression of c-MYC is suppressed by fusion with a cell that regulates MYC normally. In addition, transfer chromosome 5 by microcell fusion results in suppression of deregulated expression. Suppressed cells are not longer tumorigenic in nude mice. Loss of the transferred chromosome results in reexpression of the tumorigenic phenotype and in constitutive elevated expression of MYC. These data indicate that function of a tumor-suppressor gene on chromosome 5 is necessary for the regulated expression of MYC in at least some colon cells. Loss of this suppressor results in deregulated MYC expression and is a necessary, but most likely not sufficient, event for the expression of the tumorigenic phenotype in a subset of colon carcinomas.

OSTI ID:
5560508
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 89:4; ISSN 0027-8424; ISSN PNASA
Country of Publication:
United States
Language:
English

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