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Common and distinct features of mammary tumors driven by Pten-deletion or activating Pik3ca mutation

Jeff C Liu1, Dong-Yu Wang2,3, Sean E Egan4,5

  • 1Division of Advanced Diagnostics, Toronto General Research Institute - University Health Network, Toronto, Ontario, Canada.

Oncotarget
|January 28, 2016
PubMed

Insights

Loss of PTEN and activation of PIK3CA both increase phosphatidylinositol (3, 4, 5)-trisphosphate) (PIP3) levels in mouse mammary tumors. These genetic changes result in distinct cancer signaling profiles, potentially affecting tumor development and treatment response.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • PTEN loss and PIK3CA activation are common in cancer, both leading to increased phosphatidylinositol (3, 4, 5)-trisphosphate (PIP3) signaling.
  • Distinct biochemical functions of PTEN and PIK3CA beyond PIP3 regulation are not well understood in vivo.

Purpose of the Study:

  • To directly compare cancer signaling in mammary tumors with PTEN loss versus PIK3CA activation in mice.
  • To elucidate the in vivo consequences of PTEN loss and PIK3CA activation beyond PIP3 regulation.

Main Methods:

  • Utilized MMTV-Cre:Ptenf/f and MMTV-Cre:Pik3ca(LSL-H1047R) mouse models for mammary tumor generation.
  • Employed unsupervised hierarchical clustering to analyze tumor subtypes.
  • Conducted Gene Set Enrichment Analysis (GSEA) to compare signaling pathway profiles.

Main Results:

  • MMTV-Cre:Pik3ca(LSL-H1047R) tumors segregated into two distinct groups: squamous-likeEx and class14(Ex).
  • MMTV-Cre:Ptenf/f tumors clustered with PIK3CA(H1047R) class14(Ex) tumors, showing a 'luminal' expression profile.
  • GSEA revealed similar signaling pathway profiles between Pten(Δ) and PIK3CA(H1047R) class14(Ex) tumors, with notable differences in PI3K and EGFR signaling.

Conclusions:

  • PTEN loss and PIK3CA activation in mammary tumors lead to distinct, discernible signaling differences.
  • These differences in cancer signaling may influence tumorigenesis and response to cancer therapies.
  • Further investigation into these distinct pathways is warranted for therapeutic targeting.
Keywords:
PIK3CAPTENbioinformaticsbreast cancermouse models

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