Disabled-2 Mediates c-Fos Suppression and the Cell Growth Regulatory Activity of Retinoic Acid in Embryonic Carcinoma Cells

Elizabeth R. Smith, Callinice D. Capo-Chichi, Junqi He, Jennifer L. Smedberg, Dong Hua Yang, Amanda H. Prowse, Andrew K. Godwin, Thomas C. Hamilton, Xiangxi Xu

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

F9 embryonic stem cell-like teratocarcinoma cells are widely used to study early embryonic development and cell differentiation. The cells can be induced by retinoic acid to undergo endodermal differentiation. The retinoic acid-induced differentiation accompanies cell growth suppression, and thus, F9 cells are also often used as a model for analysis of retinoic acid biological activity. We have recently shown that MAPK activation and c-Fos expression are uncoupled in F9 cells upon retinoic acid-induced endodermal differentiation. The expression of the candidate tumor suppressor Disabled-2 is induced and correlates with cell growth suppression in F9 cells. We were not able to establish stable Disabled-2 expression by cDNA transfection in F9 cells without induction of spontaneous cell differentiation. Transient transfection of Dab2 by adenoviral vector nevertheless suppresses Elk-1 phosphorylation, c-Fos expression, and cell growth. In PA-1, another teratocarcinoma cell line of human origin that has no or very low levels of Disabled-2, retinoic acid fails to induce Disabled-2, correlating with a lack of growth suppression, although PA-1 is responsive to retinoic acid in morphological change. Transfection and expression of Disabled-2 in PA-1 cells mimic the effects of retinoic acid on growth suppression; the Disabled-2-expressing cells reach a much lower saturation density, and serum-stimulated c-Fos expression is greatly suppressed and disassociated from MAPK activation. Thus, Dab2 is one of the principal genes induced by retinoic acid involved in cell growth suppression, and expression of Dab2 alone is sufficient for uncoupling of MAPK activation and c-Fos expression. Resistance to retinoic acid regulation in PA-1 cells likely results from defects in retinoic acid up-regulation of Dab2 expression.

Original languageEnglish
Pages (from-to)47303-47310
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number50
DOIs
StatePublished - Dec 14 2001
Externally publishedYes

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Cell growth
Tretinoin
Cells
Carcinoma
Growth
Teratocarcinoma
Chemical activation
Transfection
Cell Differentiation
Phosphorylation
Bioactivity
Stem cells
Embryonic Stem Cells
Tumors
Complementary DNA
Genes
Embryonic Development
Up-Regulation
Defects

ASJC Scopus subject areas

  • Biochemistry

Cite this

Disabled-2 Mediates c-Fos Suppression and the Cell Growth Regulatory Activity of Retinoic Acid in Embryonic Carcinoma Cells. / Smith, Elizabeth R.; Capo-Chichi, Callinice D.; He, Junqi; Smedberg, Jennifer L.; Yang, Dong Hua; Prowse, Amanda H.; Godwin, Andrew K.; Hamilton, Thomas C.; Xu, Xiangxi.

In: Journal of Biological Chemistry, Vol. 276, No. 50, 14.12.2001, p. 47303-47310.

Research output: Contribution to journalArticle

Smith, ER, Capo-Chichi, CD, He, J, Smedberg, JL, Yang, DH, Prowse, AH, Godwin, AK, Hamilton, TC & Xu, X 2001, 'Disabled-2 Mediates c-Fos Suppression and the Cell Growth Regulatory Activity of Retinoic Acid in Embryonic Carcinoma Cells', Journal of Biological Chemistry, vol. 276, no. 50, pp. 47303-47310. https://doi.org/10.1074/jbc.M106158200
Smith, Elizabeth R. ; Capo-Chichi, Callinice D. ; He, Junqi ; Smedberg, Jennifer L. ; Yang, Dong Hua ; Prowse, Amanda H. ; Godwin, Andrew K. ; Hamilton, Thomas C. ; Xu, Xiangxi. / Disabled-2 Mediates c-Fos Suppression and the Cell Growth Regulatory Activity of Retinoic Acid in Embryonic Carcinoma Cells. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 50. pp. 47303-47310.
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abstract = "F9 embryonic stem cell-like teratocarcinoma cells are widely used to study early embryonic development and cell differentiation. The cells can be induced by retinoic acid to undergo endodermal differentiation. The retinoic acid-induced differentiation accompanies cell growth suppression, and thus, F9 cells are also often used as a model for analysis of retinoic acid biological activity. We have recently shown that MAPK activation and c-Fos expression are uncoupled in F9 cells upon retinoic acid-induced endodermal differentiation. The expression of the candidate tumor suppressor Disabled-2 is induced and correlates with cell growth suppression in F9 cells. We were not able to establish stable Disabled-2 expression by cDNA transfection in F9 cells without induction of spontaneous cell differentiation. Transient transfection of Dab2 by adenoviral vector nevertheless suppresses Elk-1 phosphorylation, c-Fos expression, and cell growth. In PA-1, another teratocarcinoma cell line of human origin that has no or very low levels of Disabled-2, retinoic acid fails to induce Disabled-2, correlating with a lack of growth suppression, although PA-1 is responsive to retinoic acid in morphological change. Transfection and expression of Disabled-2 in PA-1 cells mimic the effects of retinoic acid on growth suppression; the Disabled-2-expressing cells reach a much lower saturation density, and serum-stimulated c-Fos expression is greatly suppressed and disassociated from MAPK activation. Thus, Dab2 is one of the principal genes induced by retinoic acid involved in cell growth suppression, and expression of Dab2 alone is sufficient for uncoupling of MAPK activation and c-Fos expression. Resistance to retinoic acid regulation in PA-1 cells likely results from defects in retinoic acid up-regulation of Dab2 expression.",
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AU - Smith, Elizabeth R.

AU - Capo-Chichi, Callinice D.

AU - He, Junqi

AU - Smedberg, Jennifer L.

AU - Yang, Dong Hua

AU - Prowse, Amanda H.

AU - Godwin, Andrew K.

AU - Hamilton, Thomas C.

AU - Xu, Xiangxi

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