Akt1 and Akt2 play distinct roles in the initiation and metastatic phases of mammary tumor progression

Rachelle L. Dillon, Richard Marcotte, Bryan T. Hennessy, James R. Woodgett, Gordon Mills, William J. Muller

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

The phosphatidylinositol 3-kinase (PI3K)/Akt survival pathway is often dysregulated in cancer. Our previous studies have shown that coexpression of activated Akt1 with activated ErbB2 or polyoma virus middle T antigen uncoupled from the PI3K pathway (PyVmT Y315/322F) accelerates mammary tumor development but cannot rescue the metastatic phenotype associated with these models. Here, we report the generation of transgenic mice expressing activated Akt2 in the mammary epithelium. Like the mouse mammary tumor virus-Akt1 strain, mammary-specific expression of Akt2 delayed mammary gland involution. However, in contrast to Akt1, coexpression of Akt2 with activated ErbB2 or PyVmT Y315/322F in the mammary glands of transgenic mice did not affect the latency of tumor development. Strikingly, Akt2 coexpresssion markedly increased the incidence of pulmonary metastases in both tumor models, demonstrating a unique role in tumor progression. Together, these observations argue that these highly conserved kinases have distinct biological and biochemical outputs that play opposing roles in mammary tumor induction and metastasis.

Original languageEnglish (US)
Pages (from-to)5057-5064
Number of pages8
JournalCancer Research
Volume69
Issue number12
DOIs
StatePublished - Jun 15 2009
Externally publishedYes

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Phosphatidylinositol 3-Kinase
Breast Neoplasms
Human Mammary Glands
Transgenic Mice
Neoplasms
Breast
Neoplasm Metastasis
Mouse mammary tumor virus
Polyomavirus
Viral Tumor Antigens
Phosphotransferases
Epithelium
Phenotype
Lung
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Akt1 and Akt2 play distinct roles in the initiation and metastatic phases of mammary tumor progression. / Dillon, Rachelle L.; Marcotte, Richard; Hennessy, Bryan T.; Woodgett, James R.; Mills, Gordon; Muller, William J.

In: Cancer Research, Vol. 69, No. 12, 15.06.2009, p. 5057-5064.

Research output: Contribution to journalArticle

Dillon, Rachelle L. ; Marcotte, Richard ; Hennessy, Bryan T. ; Woodgett, James R. ; Mills, Gordon ; Muller, William J. / Akt1 and Akt2 play distinct roles in the initiation and metastatic phases of mammary tumor progression. In: Cancer Research. 2009 ; Vol. 69, No. 12. pp. 5057-5064.
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