Expression of PIK3CA mutant E545K in the mammary gland induces heterogeneous tumors but is less potent than mutant H1047R

D. S. Meyer, S. Koren, C. Leroy, H. Brinkhaus, U. Müller, I. Klebba, M. Müller, Robert Cardiff, M. Bentires-Alj

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Abstract

The phosphoinositide 3-kinase (PI3K) signaling cascade is a key mediator of cellular growth, survival and metabolism and is frequently subverted in human cancer. The gene encoding for the alpha catalytic subunit of PI3K (PIK3CA) is mutated and/or amplified in ∼30% of breast cancers. Mutations in either the kinase domain (H1047R) or the helical domain (E545K) are most common and result in a constitutively active enzyme with oncogenic capacity. PIK3CA H1047R was previously demonstrated to induce tumors in transgenic mouse models; however, it was not known whether overexpression of PIK3CA E545K is sufficient to induce mammary tumors and whether tumor initiation by these two types of mutants differs. Here, we demonstrate that expression of PIK3CA E545K in the mouse mammary gland induces heterogenous mammary carcinomas but with a longer latency than PIK3CA H1047R -expressing mice. Our results suggest that the helical domain mutant PIK3CA E545K is a less potent inducer of mammary tumors due to less efficient activation of downstream Akt signaling.

Original languageEnglish (US)
Article numbere74
JournalOncogenesis
Volume2
DOIs
StatePublished - Oct 18 2013

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Human Mammary Glands
Breast Neoplasms
1-Phosphatidylinositol 4-Kinase
Neoplasms
Transgenic Mice
Catalytic Domain
Phosphotransferases
Mutation
Survival
Enzymes
Growth
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Meyer, D. S., Koren, S., Leroy, C., Brinkhaus, H., Müller, U., Klebba, I., ... Bentires-Alj, M. (2013). Expression of PIK3CA mutant E545K in the mammary gland induces heterogeneous tumors but is less potent than mutant H1047R. Oncogenesis, 2, [e74]. https://doi.org/10.1038/oncsis.2013.38

Expression of PIK3CA mutant E545K in the mammary gland induces heterogeneous tumors but is less potent than mutant H1047R. / Meyer, D. S.; Koren, S.; Leroy, C.; Brinkhaus, H.; Müller, U.; Klebba, I.; Müller, M.; Cardiff, Robert; Bentires-Alj, M.

In: Oncogenesis, Vol. 2, e74, 18.10.2013.

Research output: Contribution to journalArticle

Meyer, DS, Koren, S, Leroy, C, Brinkhaus, H, Müller, U, Klebba, I, Müller, M, Cardiff, R & Bentires-Alj, M 2013, 'Expression of PIK3CA mutant E545K in the mammary gland induces heterogeneous tumors but is less potent than mutant H1047R', Oncogenesis, vol. 2, e74. https://doi.org/10.1038/oncsis.2013.38
Meyer, D. S. ; Koren, S. ; Leroy, C. ; Brinkhaus, H. ; Müller, U. ; Klebba, I. ; Müller, M. ; Cardiff, Robert ; Bentires-Alj, M. / Expression of PIK3CA mutant E545K in the mammary gland induces heterogeneous tumors but is less potent than mutant H1047R. In: Oncogenesis. 2013 ; Vol. 2.
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