TGFalpha is required for full expression of the transformed growth phenotype of NIH 3T3 cells overexpressing ornithine decarboxylase
| Autor: | Jeffrey A. Moshier, Adhip P.N. Majumdar, Hairong Geng, Magdalena Skunca, Julie Dosescu, Paul H. Naylor |
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| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
genetic structures integumentary system Cell growth fungi Contact inhibition General Medicine Transfection 3T3 Cells Biology Transforming Growth Factor alpha Ornithine Decarboxylase 3T3 cells ErbB Receptors Mice medicine.anatomical_structure Cell Transformation Neoplastic Phenotype Growth factor receptor Epidermal growth factor Cell culture medicine Cancer research Animals Tyrosine kinase |
| Zdroj: | Carcinogenesis. 21(4) |
| ISSN: | 0143-3334 |
| Popis: | 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 TGFalpha in mediating the EGFR-dependent transformation of NIH 3T3 cells by ODC. Disruption of EGFR-TGFalpha interactions either by deleting EGFR, by treatment with anti-TGFalpha neutralizing antibody or by transfection with a TGFalpha 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-TGFalpha interactions than anchorage-independent growth in ODC-overexpressing cells. ODC overexpression does not alter the amount, localization or secretion of TGFalpha. Thus, TGFalpha 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. |
| Databáze: | OpenAIRE |
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