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PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma

Author:
  • Lao Saal
  • Karolina Holm
  • M Maurer
  • L Memeo
  • T Su
  • XM Wang
  • JS Yu
  • Per Malmström
  • M Mansukhani
  • Jens Enoksson
  • H Hibshoosh
  • Åke Borg
  • R Parsons
Publishing year: 2005
Language: English
Pages: 2554-2559
Publication/Series: Cancer Research
Volume: 65
Issue: 7
Document type: Journal article
Publisher: American Association for Cancer Research Inc.

Abstract english

Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) occurs frequently in human cancer. We identified PIK3CA mutations in 26% of 342 human breast tumor samples and cell lines at about equal frequency in tumor stages I to IV. To investigate the relationship between PTEN and PIK3CA, we generated a cohort of tumors that had lost PTEN expression and compared it with a matched control set that had retained PTEN. A highly significant association between PIK3CA mutations and retention of PTEN protein expression was observed. In addition, PIK3CA mutations were associated with expression of estrogen and progesterone receptors (ER/PR), lymph node metastasis, and ERBB2 overexpression. The fact that PIK3CA mutations and PTEN loss are nearly mutually exclusive implies that deregulated phosphatidylinositol-3,4,5-triphosphate WIN is critical for tumorigenesis in a significant fraction of breast cancers and that loss Of PIP3 homeostasis by abrogation of either PIK3CA or PTEN relieves selective pressure for targeting of the other gene. The correlation of PIK3CA mutation to ER/PR-positive tumors and PTEN loss to ER/PR-negative tumors argues for disparate branches of tumor evolution. Furthermore, the association between ERBB2 overexpression and PIK3CA mutation implies that more than one input activating the PI3K/AKT pathway may be required to overcome intact PTEN. Thus, mutation of PIK3CA is frequent, occurs early in carcinoma development, and has prognostic and therapeutic implications.

Keywords

  • Cancer and Oncology

Other

Published
  • ISSN: 1538-7445
Åke Borg
Åke Borg
E-mail: ake [dot] borg [at] med [dot] lu [dot] se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90