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Constitutively activated PI3K accelerates tumor initiation and modifies histopathology of breast cancer.

Publication ,  Journal Article
Sheen, MR; Marotti, JD; Allegrezza, MJ; Rutkowski, M; Conejo-Garcia, JR; Fiering, S
Published in: Oncogenesis
October 31, 2016

The gene encoding phosphatidylinositol 3-kinase catalytic subunit α-isoform (PIK3CA, p110α) is frequently activated by mutation in human cancers. Based on detection in some breast cancer precursors, PIK3CA mutations have been proposed to have a role in tumor initiation. To investigate this hypothesis, we generated a novel mouse model with a Cre-recombinase regulated allele of p110α (myristoylated-p110α, myr-p110α) along with p53fl/fl deletion and KrasG12D also regulated by Cre-recombinase. After instillation of adenovirus-expressing Cre-recombinase into mammary ducts, we found that myr-p110α accelerated breast tumor initiation in a copy number-dependent manner. Breast tumors induced by p53fl/fl;KrasG12D with no or one copy of myr-p110α had predominantly sarcomatoid features, whereas two copies of myr-p110α resulted in tumors with a carcinoma phenotype. This novel model provides experimental support for importance of active p110α in breast tumor initiation, and shows that the amount of PI3K activity can affect the rate of tumor initiation and modify the histological phenotype of breast cancer.

Duke Scholars

Published In

Oncogenesis

DOI

ISSN

2157-9024

Publication Date

October 31, 2016

Volume

5

Issue

10

Start / End Page

e267

Location

United States

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
  • 0604 Genetics
  • 0601 Biochemistry and Cell Biology
 

Citation

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ICMJE
MLA
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Sheen, M. R., Marotti, J. D., Allegrezza, M. J., Rutkowski, M., Conejo-Garcia, J. R., & Fiering, S. (2016). Constitutively activated PI3K accelerates tumor initiation and modifies histopathology of breast cancer. Oncogenesis, 5(10), e267. https://doi.org/10.1038/oncsis.2016.65
Sheen, M. R., J. D. Marotti, M. J. Allegrezza, M. Rutkowski, J. R. Conejo-Garcia, and S. Fiering. “Constitutively activated PI3K accelerates tumor initiation and modifies histopathology of breast cancer.Oncogenesis 5, no. 10 (October 31, 2016): e267. https://doi.org/10.1038/oncsis.2016.65.
Sheen MR, Marotti JD, Allegrezza MJ, Rutkowski M, Conejo-Garcia JR, Fiering S. Constitutively activated PI3K accelerates tumor initiation and modifies histopathology of breast cancer. Oncogenesis. 2016 Oct 31;5(10):e267.
Sheen, M. R., et al. “Constitutively activated PI3K accelerates tumor initiation and modifies histopathology of breast cancer.Oncogenesis, vol. 5, no. 10, Oct. 2016, p. e267. Pubmed, doi:10.1038/oncsis.2016.65.
Sheen MR, Marotti JD, Allegrezza MJ, Rutkowski M, Conejo-Garcia JR, Fiering S. Constitutively activated PI3K accelerates tumor initiation and modifies histopathology of breast cancer. Oncogenesis. 2016 Oct 31;5(10):e267.

Published In

Oncogenesis

DOI

ISSN

2157-9024

Publication Date

October 31, 2016

Volume

5

Issue

10

Start / End Page

e267

Location

United States

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
  • 0604 Genetics
  • 0601 Biochemistry and Cell Biology