Activation of phosphatidylinositol 3-kinase (PI3K) as a predictor of clinical outcome in breast cancer patients

R. F. Swaby, A. A. Sahin, R. Broaddus, Y. Lu, A. Eder, A. Thornton, Gordon Mills

Research output: Contribution to journalArticle

Abstract

Phosphorylation of membrane phosphatidylinositols by phosphatidylinositol 3-kinase (PI3K) plays a pivotal role in the control of cell proliferation, differentiation, senescence, cytoskeletal organization, motility, metastases, invasion, angiogenesis, and cell survival. This suggests that PI3K may play a critical role in cell growth regulation and potentially tumorigenesis. PI3K phosphorylates membrane phosphatidylinositol bisphosphate-4,5 (PtdIns-4,5) creating phosphatidylinositol-3,4,5 (PtdIns-3,4,5). 3-phosphorylated PtdIns recruit AKT to the cell membrane where it is then phosphorylated by PDK1 and PDK2 to its activated form. Several lines of evidence suggest that activation of AKT is involved in breast cancer development. These include DNA and RNA amplification of AKT in breast cancer tissue samples. Additionally, PTEN/MMAC1, which functions as a tumor suppressor by dephosphorylating PtdIns-3,4,5 thereby rendering it unable to activate AKT, has been found to be mutated in breast cancer, both sporadic and associated with Cowden's Syndrome. We assessed whether PI3K activation and PTEN loss of activity are correlated with clinical outcome in patients with breast cancer. It has previously been difficult to measure cellular PI3K activity from cultured cells and biopsies. We have developed an immunohistochemical technique to stain for the presence of PtdIns-3,4,5, demonstrating PI3K activation in the breast cancer cell line MDA-MB468, and are retrospectively testing archived tissue samples from breast cancer patients. We report the presence of PI3K activation, and its' downstream effector, AKT, with respect to patient outcome.

Original languageEnglish (US)
Number of pages1
JournalBreast Cancer Research and Treatment
Volume69
Issue number3
StatePublished - Jan 1 2001
Externally publishedYes

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Phosphatidylinositol 3-Kinase
Phosphatidylinositols
Breast Neoplasms
Multiple Hamartoma Syndrome
Membranes
Cell Differentiation
Cultured Cells
Cell Survival
Carcinogenesis
Coloring Agents
Phosphorylation
Cell Proliferation
Cell Membrane
RNA
Neoplasm Metastasis
Biopsy
Cell Line
DNA
Growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Activation of phosphatidylinositol 3-kinase (PI3K) as a predictor of clinical outcome in breast cancer patients. / Swaby, R. F.; Sahin, A. A.; Broaddus, R.; Lu, Y.; Eder, A.; Thornton, A.; Mills, Gordon.

In: Breast Cancer Research and Treatment, Vol. 69, No. 3, 01.01.2001.

Research output: Contribution to journalArticle

Swaby, R. F. ; Sahin, A. A. ; Broaddus, R. ; Lu, Y. ; Eder, A. ; Thornton, A. ; Mills, Gordon. / Activation of phosphatidylinositol 3-kinase (PI3K) as a predictor of clinical outcome in breast cancer patients. In: Breast Cancer Research and Treatment. 2001 ; Vol. 69, No. 3.
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