Smads mediate signaling of the TGFβ superfamily in normal keratinocytes but are lost during skin chemical carcinogenesis

Wei He, Tongyu Wikramanayake, Daniel A. Smith, Todd E. Myers, Xiao Jing Wang

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The Smads are the signaling mediators of the TGFβ superfamily. In the present study, we examined Smad expression in mouse epidermis and chemically-induced skin tumors. Mutations in Smad2 and -4 genes were also screened. Transcripts of Smad1 through -5 were constantly expressed in the epidermis regardless of changes in TGFβ signaling, state of differentiation and stages of carcinogenesis. Smad7 transcripts were barely detectable in keratinocytes, but were induced by TGFβ1 treatment and in chemically-induced skin tumors. At the protein level, Smad1 was detected throughout the epidermis, whereas Smad2 through -5 exhibited greater levels in suprabasal layers than basal keratinocytes. In cultured keratinocytes, Smad2, -3 and -4 underwent nuclear translocation upon TGFβ1 treatment. Further-more, nuclear translocation of Smads correlated with decreased BrdU labeling in proliferative keratinocytes. Although no mutations were detected in the Smad2 and -4 genes in tumors, proteins of Smad1 through -5 were partially or completely lost in carcinomas. These data document that Smads are expressed at high levels in the epidermis and mediate signaling of the TGFβ1 super-family. During skin carcinogenesis, loss of Smad1 through -5 and overexpression of Smad7 may contribute to the loss of growth inhibition mediated by TGFβ superfamily members, thus resulting in tumor progression.

Original languageEnglish
Pages (from-to)471-483
Number of pages13
JournalOncogene
Volume20
Issue number4
DOIs
StatePublished - Jan 25 2001
Externally publishedYes

Fingerprint

Keratinocytes
Epidermis
Carcinogenesis
Skin
Smad1 Protein
Neoplasms
Mutation
Bromodeoxyuridine
Genes
Carcinoma
Growth
Proteins

Keywords

  • Growth inhibition
  • Keratinocytes
  • Skin chemical carcinogenesis
  • Transforming growth factor β
  • Tumor progression

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Smads mediate signaling of the TGFβ superfamily in normal keratinocytes but are lost during skin chemical carcinogenesis. / He, Wei; Wikramanayake, Tongyu; Smith, Daniel A.; Myers, Todd E.; Wang, Xiao Jing.

In: Oncogene, Vol. 20, No. 4, 25.01.2001, p. 471-483.

Research output: Contribution to journalArticle

He, Wei ; Wikramanayake, Tongyu ; Smith, Daniel A. ; Myers, Todd E. ; Wang, Xiao Jing. / Smads mediate signaling of the TGFβ superfamily in normal keratinocytes but are lost during skin chemical carcinogenesis. In: Oncogene. 2001 ; Vol. 20, No. 4. pp. 471-483.
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