Skp2 is necessary for Myc-induced keratinocyte proliferation but dispensable for Myc oncogenic activity in the oral epithelium

Christopher Sistrunk, Everardo MacIas, Keiichi Nakayama, Yongbaek Kim, Marcelo L. Rodriguez-Puebla

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

抄録

The proto-oncogene c-Myc encodes a transcription factor that is implicated in the regulation of cellular proliferation, differentiation, and apoptosis. Myc accelerates the rate of cell proliferation, at least in part, through its ability to down-regulate the expression of the cell cycle inhibitor p27 Kip1. Moreover, p27Kip1 protein levels are regulated by ubiquitin-mediated turnover, leading to destruction by the E3 ubiquitin ligase SCFSkp2. Therefore, we hypothesize that a lack of Skp2 expression should lead to increased p27Kip1 levels and further inhibition of Myc-mediated proliferation and tumorigenesis. Myc expression in epithelial tissues of transgenic mice (K5-Myc) led to increased keratinocyte proliferation and the development of spontaneous tumors within the oral cavity. We generated K5-Myc- transgenic mice in an Skp2-null background. Consistent with our hypothesis, we found that Myc-mediated keratinocyte hyperproliferation was abolished by the loss of Skp2. However, Skp2 ablation did not affect Myc-driven tumorigenesis because the incidence, latency, and degree of differentiation of oral tumors were identical between K5-Myc/Skp2+/+ and K5-Myc/Skp2-/- mice. Altogether, these findings suggest that Skp2 and p27Kip1 are critical for Myc-driven keratinocyte proliferation; however, Myc-mediated tumorigenesis in the oral epithelium is independent of the Skp2-p27Kip1 axis.

元の言語英語
ページ(範囲)2470-2477
ページ数8
ジャーナルAmerican Journal of Pathology
178
発行部数6
DOI
出版物ステータス出版済み - 6 2011

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Keratinocytes
Carcinogenesis
Epithelium
Transgenic Mice
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p27
myc Genes
Ubiquitin-Protein Ligases
Ubiquitin
Mouth
Neoplasms
Cell Cycle
Transcription Factors
Down-Regulation
Apoptosis
Incidence

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

これを引用

Skp2 is necessary for Myc-induced keratinocyte proliferation but dispensable for Myc oncogenic activity in the oral epithelium. / Sistrunk, Christopher; MacIas, Everardo; Nakayama, Keiichi; Kim, Yongbaek; Rodriguez-Puebla, Marcelo L.

:: American Journal of Pathology, 巻 178, 番号 6, 06.2011, p. 2470-2477.

研究成果: ジャーナルへの寄稿記事

Sistrunk, Christopher ; MacIas, Everardo ; Nakayama, Keiichi ; Kim, Yongbaek ; Rodriguez-Puebla, Marcelo L. / Skp2 is necessary for Myc-induced keratinocyte proliferation but dispensable for Myc oncogenic activity in the oral epithelium. :: American Journal of Pathology. 2011 ; 巻 178, 番号 6. pp. 2470-2477.
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