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Journal of cellular biochemistry
Oct, 2012;113 (10): 3069-85.

Transforming growth factor-β activates c-Myc to promote palatal growth.

Xiujuan Zhu, Ferhat Ozturk, Changchih Liu, Gregory G Oakley, Ali Nawshad
Author Information
  1. Xiujuan Zhu: Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68512, USA.
PMID: 22573578 DOI: 10.1002/jcb.24184

Abstract

During palatogenesis, the palatal mesenchyme undergoes increased cell proliferation resulting in palatal growth, elevation and fusion of the two palatal shelves. Interestingly, the palatal mesenchyme expresses all three transforming growth factor (TGF) β isoforms (1, 2, and 3) throughout these steps of palatogenesis. However, the role of TGFβ in promoting proliferation of palatal mesenchymal cells has never been explored. The purpose of this study was to identify the effect of TGFβ on human embryonic palatal mesenchymal (HEPM) cell proliferation. Our results showed that all isoforms of TGFβ, especially TGFβ3, increased HEPM cell proliferation by up-regulating the expression of cyclins and cyclin-dependent kinases as well as c-Myc oncogene. TGFβ activated both Smad-dependent and Smad-independent pathways to induce c-Myc gene expression. Furthermore, TBE1 is the only functional Smad binding element (SBE) in the c-Myc promoter and Smad4, activated by TGFβ, binds to the TBE1 to induce c-Myc gene activity. We conclude that HEPM proliferation is manifested by the induction of c-Myc in response to TGFβ signaling, which is essential for complete palatal confluency. Our data highlights the potential role of TGFβ as a therapeutic molecule to correct cleft palate by promoting growth.

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Grants

  1. R01 DE017986/NIDCR NIH HHS
  2. R01DE017986/NIDCR NIH HHS

MeSH Term

Animals
Apoptosis
Cell Cycle
Cell Cycle Proteins
Cell Line
Cell Proliferation
Cyclin-Dependent Kinases
Female
Gene Expression Regulation, Developmental
Humans
Male
Mesoderm
Mice
Mice, Transgenic
Palate
Pregnancy
Promoter Regions, Genetic
Protein Isoforms
Proto-Oncogene Proteins c-myc
Recombinant Proteins
Signal Transduction
Smad4 Protein
Transcriptional Activation
Transfection
Transforming Growth Factor beta3

Chemicals

Cell Cycle Proteins
MYC protein, human
Protein Isoforms
Proto-Oncogene Proteins c-myc
Recombinant Proteins
SMAD4 protein, human
Smad4 Protein
Transforming Growth Factor beta3
Cyclin-Dependent Kinases
Journal Article Research Support, N.I.H., Extramural

Word Cloud

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