RGD Reference Report - Akt1 and akt2 play distinct roles in the initiation and metastatic phases of mammary tumor progression. - Rat Genome Database

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Akt1 and akt2 play distinct roles in the initiation and metastatic phases of mammary tumor progression.

Authors: Dillon, RL  Marcotte, R  Hennessy, BT  Woodgett, JR  Mills, GB  Muller, WJ 
Citation: Dillon RL, etal., Cancer Res. 2009 Jun 15;69(12):5057-64. Epub 2009 Jun 2.
RGD ID: 2315599
Pubmed: PMID:19491266   (View Abstract at PubMed)
PMCID: PMC4151524   (View Article at PubMed Central)
DOI: DOI:10.1158/0008-5472.CAN-08-4287   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Neoplasm Metastasis  IMP 2315599associated with Mammary Neoplasms and ExperimentalRGD 
Neoplasm Metastasis  ISOAKT2 (Homo sapiens)2315599; 2315599associated with Mammary Neoplasms and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Akt2  (AKT serine/threonine kinase 2)

Genes (Mus musculus)
Akt2  (thymoma viral proto-oncogene 2)

Genes (Homo sapiens)
AKT2  (AKT serine/threonine kinase 2)


Additional Information