Functional roles of Akt signaling in mouse skin tumorigenesis

Carmen Segrelles, Sergio Ruiz, Paloma Perez, Cristina Murga, Mirentxu Santos, Irina V. Budunova, Jesus Martínez, Fernando Larcher, Thomas J. Slaga, J. Silvio Gutkind, Jose L. Jorcano, Jesus M. Paramio

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

Abstract

The mouse skin carcinogenesis protocol is a unique model for understanding the molecular events leading to oncogenic transformation. Mutations in the Ha-ras gene, and the presence of functional cyclin D1 and the EGF receptor, have proven to be important in this system. However, the signal transduction pathways connecting these elements during mouse skin carcinogenesis are poorly understood. This paper studies the relevance of the Akt and ERK pathways in the different stages of chemically induced mouse skin tumors. Akt activity increases throughout the entire process, and its early activation is detected prior to increased cyclin D1 expression. ERK activity rises only during the later stages of malignant conversion. The observed early increase in Akt activity appears to be due to raised PI-3K activity. Other factors acting on Akt such as ILK activation and decreased PTEN phosphatase activity appear to be involved at the conversion stage. To further confirm the involvement of Akt in this process, PB keratinocytes were transfected with Akt and subsequently injected into nude mice. The expression of Akt accelerates tumorigenesis and contributes to increased malignancy of these keratinocytes as demonstrated by the rate of appearance, the growth and the histological characteristics of the tumors. Collectively, these data provide evidence that Akt activation is one of the key elements during the different steps of mouse skin tumorigenesis.

Original languageEnglish (US)
Pages (from-to)53-64
Number of pages12
JournalOncogene
Volume21
Issue number1
DOIs
StatePublished - 2002

Keywords

  • Akt
  • PTEN
  • Ras
  • Signal transduction
  • Skin carcinogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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