The capacity for growth stimulation by TGFβ1 seen only in advanced colon cancers cannot be ascribed to mutations in APC, DCC, p53 or ras

Fei Huang, Stephen Hsu, Zhongfa Yan, Sid Winawer, Eileen Friedman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Human colon cancer development is associated with the accumulation of mutations and deletions in the suppressor genes DCC, APC and p53 and mutations in the dominant oncogene K-ras, with loss of wild type alleles. In earlier studies we had observed that about half of the resected human colon cancers placed into primary culture were growth stimulated by TGFβ1. This group included the more advanced cancers which were either poorly differentiated primary-site cancers or metastases. In contract, the more differentiated colon cancers were inhibited or unaffected by TGFβ1, indicating that a switch in response to TGFβ1 occurs during colon cancer progression. Different sublines of the HT29 colon carcinoma cell line model the resected cancers, responding to TGFβ1 by proliferation, inhibition or no growth modulation. The current study shows that while the poorly differentiated, TGFβ1-stimulated sublines are most tumorigenic, all the sublines have the same spectrum of mutations: truncating mutations in both APC (adenomatous polyposis coli) alleles, no activated ras genes, mutated and thus overexpressed p53, and very low expression of DCC compared to normal colon cells. Genes other than the four already implicated in colon carcinoma evolution are responsible for the mitogenic response to TGFβ1 found in the more advanced cancers.

Original languageEnglish (US)
Pages (from-to)3701-3706
Number of pages6
JournalOncogene
Volume9
Issue number12
StatePublished - Dec 1 1994

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Adenomatous Polyposis Coli
Colonic Neoplasms
Colon
Mutation
ras Genes
Growth
Neoplasms
Alleles
Suppressor Genes
Carcinoma
Sequence Deletion
Contracts
Neoplasm Metastasis
Cell Line
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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The capacity for growth stimulation by TGFβ1 seen only in advanced colon cancers cannot be ascribed to mutations in APC, DCC, p53 or ras. / Huang, Fei; Hsu, Stephen; Yan, Zhongfa; Winawer, Sid; Friedman, Eileen.

In: Oncogene, Vol. 9, No. 12, 01.12.1994, p. 3701-3706.

Research output: Contribution to journalArticle

Huang, Fei ; Hsu, Stephen ; Yan, Zhongfa ; Winawer, Sid ; Friedman, Eileen. / The capacity for growth stimulation by TGFβ1 seen only in advanced colon cancers cannot be ascribed to mutations in APC, DCC, p53 or ras. In: Oncogene. 1994 ; Vol. 9, No. 12. pp. 3701-3706.
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