Tumor suppressor and oncogene actions of TGFBl occur early in skin carcinogenesis and are mediated by Smad3

Dong Soon Bae, Nicholas Blazanin, Mathew Licata, Jessica Lee, Adam Bleier Glick

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Interactions between TGFB1 and ras signaling pathways play an important role in cancer development. Here we show that in primary mouse keratinocytes, v-rasHa does not block the early biochemical events of TGFB1 signal transduction but does alter global TGFB1 mediated gene expression in a gene specific manner. Expression of Smad3 dependent TGFP1 early response genes and the TGFP1 cytostatic gene expression response were not altered by v-rasHa consistent with an intact TGFP1 growth arrest. However, TGFP1 and v-rasHa cause significant alteration in genes regulating matrix remodeling as the TGFP1 induction of extracellular matrix genes was blocked by v-rasHa but specific matrix proteases associated with cancer progression were elevated. Smad3 deletion in keratinocytes repressed normal differentiation maker expression and caused expression of Keratin 8 a simple epithelial keratin and marker of malignant conversion. Smad3 was required for the TGFP1 cytostatic response in v-rasHa keratinocytes, but also for protease induction, keratinocyte attachment and migration. These results show that pro-oncogenic activities of TGFP1 can occur early in carcinogenesis before loss of its tumor suppressive function and that selective regulation rather than complete inactivation of Smad3 function may be crucial for tumor progression.

Original languageEnglish (US)
Pages (from-to)441-453
Number of pages13
JournalMolecular Carcinogenesis
Volume48
Issue number5
DOIs
StatePublished - May 1 2009

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Keratinocytes
Oncogenes
Carcinogenesis
Skin
Cytostatic Agents
Genes
Neoplasms
Peptide Hydrolases
Keratin-8
Gene Expression
Keratins
Extracellular Matrix
Signal Transduction
Growth

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Molecular Biology

Cite this

Bae, Dong Soon ; Blazanin, Nicholas ; Licata, Mathew ; Lee, Jessica ; Glick, Adam Bleier. / Tumor suppressor and oncogene actions of TGFBl occur early in skin carcinogenesis and are mediated by Smad3. In: Molecular Carcinogenesis. 2009 ; Vol. 48, No. 5. pp. 441-453.
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Tumor suppressor and oncogene actions of TGFBl occur early in skin carcinogenesis and are mediated by Smad3. / Bae, Dong Soon; Blazanin, Nicholas; Licata, Mathew; Lee, Jessica; Glick, Adam Bleier.

In: Molecular Carcinogenesis, Vol. 48, No. 5, 01.05.2009, p. 441-453.

Research output: Contribution to journalArticle

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