Reconstitution of TGF-β sensitivity in the VACO-411 human colon carcinoma line by somatic cell fusion with MCF-7

June L. Traicoff, Sumudra Periyasamy, Michael G. Brattain, William Grady, Graham Casey

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

We characterized the mechanism of transforming growth factor beta (TGF-β) resistance in the VACO-411 human colon carcinoma line. VACO-411 is unique for several reasons, including having a novel mutator phenotype and wild-type p53. Like many colon tumors, VACO-411 is not growth inhibited by TGF-β. However, VACO-411 represents a subset of colon tumors that are resistant to TGF-β-mediated growth inhibition, despite the expression of functional TGF-β receptors. VACO-411 expresses cell surface TGF-β receptor types I and II, and the coding regions of these receptors are wild type. To further characterize the nature of the VACO-411 defect, we fused VACO-411 with the human breast carcinoma line MCF-7. MCF-7 is also resistant to TGF-β-mediated growth inhibition. However, unlike VACO-411, MCF-7 lacks cell surface expression of TGF-β receptor type II, but does contain an intact postreceptor signaling pathway, as shown by regeneration of TGF-β sensitivity following wild-type TGF-β receptor type II transfection. In contrast to parental VACO-411 and MCF-7, the morphologically distinct cell hybrids were growth inhibited by TGF-β. Therefore, the TGF-β defect in VACO-411 is a postreceptor, loss-of-function mutation which can be genetically complemented. The data suggest that the VACO-411 defect in TGF-β signaling will be able to be further complemented by microcell-mediated chromosome transfer.

Original languageEnglish (US)
Pages (from-to)253-259
Number of pages7
JournalJournal of Biomedical Science
Volume10
Issue number2
DOIs
StatePublished - Mar 20 2003
Externally publishedYes

Keywords

  • Cell fusions
  • Colon
  • Complementation
  • Signal transduction
  • Transforming growth factor beta

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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