Transforming Growth Factor β Isoform-specific Differences in Interactions with Type I and II Transforming Growth Factor β Receptors

Gwendolyn L. Sechrist, Kathleen M. Mulder, Guo Hao K. Zhou, Sumudra Periyasamy, Michael G. Brattain

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Here we describe human colon carcinoma cell clones, isolated from a transforming growth factor β (TGF-β)-responsive parental cell line, which display differential sensitivities to TGF β1 and TGF-β2 isoforms. In a monolayer proliferation assay, some clones were sensitive to both isoforms (IC50 = 0.1-0.6 ng/ml; S1S2) while others were resistant to both isoforms (IC50 < 5 ng/ml; R1R2). Still other clones (R1S2) were sensitive to TGF-02 (IC50 = 0.1-0.2 ng/ml), but were resistant to TGF-β1 (IC50 ≥ 5 ng/ml). In S1S2 cells, both TGF-β isoforms resulted in a repression of c-myc mRNA expression, a concentration-dependent increase in fibronec-tin levels, and an enhanced production of the colon cell differentiation marker carcinoembryonic antigen. In contrast, R1R2 cells did not display these responses, or did so only to a limited extent In R1S2 cells, TGF-β elicited these responses, yet TGF-β, was essentially without effect Receptor cross-linking experiments indicated that TGF-β resistance in this model system was not generally associated with a complete lack of expression of either type I or II receptors. Moreover, the R1S2 type clones were heterogeneous, although the majority of them displayed binding to type I receptors by TGF-β2 but not by TGF-β1,. These data suggest that either the TGF-β1 and TGF-β2 isoforms differ with respect to their ability to interact with the type I and II classes of receptors, or the TGF-β1 and TGF-β2 isoforms can interact with distinct receptor proteins of the type I and II classes in this model system.

Original languageEnglish (US)
Pages (from-to)2056-2062
Number of pages7
JournalCancer Research
Volume55
Issue number10
StatePublished - May 15 1995

Fingerprint

Growth Factor Receptors
Transforming Growth Factors
Protein Isoforms
Inhibitory Concentration 50
Differentiation Antigens
Clone Cells
Colon
Tin
Carcinoembryonic Antigen
Cell Differentiation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sechrist, G. L., Mulder, K. M., Zhou, G. H. K., Periyasamy, S., & Brattain, M. G. (1995). Transforming Growth Factor β Isoform-specific Differences in Interactions with Type I and II Transforming Growth Factor β Receptors. Cancer Research, 55(10), 2056-2062.

Transforming Growth Factor β Isoform-specific Differences in Interactions with Type I and II Transforming Growth Factor β Receptors. / Sechrist, Gwendolyn L.; Mulder, Kathleen M.; Zhou, Guo Hao K.; Periyasamy, Sumudra; Brattain, Michael G.

In: Cancer Research, Vol. 55, No. 10, 15.05.1995, p. 2056-2062.

Research output: Contribution to journalArticle

Sechrist, GL, Mulder, KM, Zhou, GHK, Periyasamy, S & Brattain, MG 1995, 'Transforming Growth Factor β Isoform-specific Differences in Interactions with Type I and II Transforming Growth Factor β Receptors', Cancer Research, vol. 55, no. 10, pp. 2056-2062.
Sechrist, Gwendolyn L. ; Mulder, Kathleen M. ; Zhou, Guo Hao K. ; Periyasamy, Sumudra ; Brattain, Michael G. / Transforming Growth Factor β Isoform-specific Differences in Interactions with Type I and II Transforming Growth Factor β Receptors. In: Cancer Research. 1995 ; Vol. 55, No. 10. pp. 2056-2062.
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