Journal Article

TGFα is required for full expression of the transformed growth phenotype of NIH 3T3 cells overexpressing ornithine decarboxylase

Hairong Geng, Paul H. Naylor, Julie Dosescu, Magdalena Skunca, Adhip P.N. Majumdar and Jeffrey A. Moshier

in Carcinogenesis

Volume 21, issue 4, pages 567-572
Published in print April 2000 | ISSN: 0143-3334
Published online April 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.4.567
TGFα is required for full expression of the transformed growth phenotype of NIH 3T3 cells overexpressing ornithine decarboxylase

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Ornithine decarboxylase (ODC) overexpressed from a heterologous promoter drives the tumorigenic transformation of NIH 3T3 cells and provides a model to investigate the underlying molecular mechanisms. These transformed cells, designated NODC cells, exhibit elevated levels of epidermal growth factor receptor (EGFR) tyrosine kinase (Tyr-k) activity relative to control transfected cells and inhibition of EGFR Tyr-k activation suppresses the transformed growth phenotype of these cells. Thus, ODC-induced transformation of NIH 3T3 cells appears to be mediated, at least in part, by enhanced signaling through the EGFR pathway. Here we extend these studies by evaluating: (i) the effects on growth regulation of overexpressing ODC in EGFR-deficient NIH 3T3 cells; (ii) the potential role of TGFα in mediating the EGFR-dependent transformation of NIH 3T3 cells by ODC. Disruption of EGFR–TGFα interactions either by deleting EGFR, by treatment with anti-TGFα neutralizing antibody or by transfection with a TGFα antisense expression vector suppressed acquisition of the full transformed growth phenotype. Specifically, the loss of contact inhibition and the capacity for clonogenic growth appear more dependent on EGFR–TGFα interactions than anchorage-independent growth in ODC-overexpressing cells. ODC overexpression does not alter the amount, localization or secretion of TGFα. Thus, TGFα is not the ODC-responsive component of the EGFR signaling pathway but appears to be critically involved in development of the transformed phenotype of NODC cells.

Keywords: DMEM, Dulbecco's modified Eagle's medium; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; FBS, fetal bovine serum; ODC, ornithine decarboxylase; PBS, phosphate-buffered saline; TGFα, transforming growth factor α; Tyr-k, tyrosine kinase.

Journal Article.  4922 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.