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Breast Cancer Research
Published in: Breast Cancer Research 1/2010

Open Access 01-02-2010 | Research article

Type I gamma phosphatidylinositol phosphate kinase modulates invasion and proliferation and its expression correlates with poor prognosis in breast cancer

Authors: Yue Sun, Dmitry A Turbin, Kun Ling, Narendra Thapa, Samuel Leung, David G Huntsman, Richard A Anderson

Published in: Breast Cancer Research | Issue 1/2010

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Abstract

Introduction

The loss of E-cadherin based cell-cell contacts and tumor cell migration to the vasculature and lymphatic system are hallmarks of metastasis of epithelial cancers. Type I gamma phosphatidylinositol phosphate kinase (PIPKIγ), an enzyme that generates phosphatidylinositol 4,5-bisphosphate (PI4,5P2) a lipid messenger and precursor to many additional second messengers, was found to regulate E-cadherin cell-cell contacts and growth factor-stimulated directional cell migration, indicating that PIPKIγ regulates key steps in metastasis. Here, we assess the expression of PIPKIγ in breast cancers and have shown that expression correlated with disease progression and outcome.

Methods

Using a tissue microarray, we analyzed 438 breast carcinomas for the levels of PIPKIγ and investigated the correlation of PIPKIγ expression with patient survival via Kaplan-Meier survival analysis. Moreover, via knockdown of the expression of PIPKIγ in cultured breast cancer cells with siRNA, the roles of PIPKIγ in breast cancer migration, invasion, and proliferation were examined.

Results

Tissue microarray data shows that ~18% of the cohort immunostained showed high expression of PIPKIγ. The Kaplan-Meier survival analysis revealed a significant inverse correlation between strong PIPKIγ expression and overall patient survival. Expression of PIPKIγ correlated positively with epidermal growth factor receptor (EGFR) expression, which regulates breast cancer progression and metastasis. In cultured breast cancer cells, PIPKIγ is required for growth factor stimulated migration, invasion, and proliferation of cells.

Conclusions

The results reveal a significant correlation between PIPKIγ expression and the progression of breast cancer. This is consistent with PIPKIγ 's role in breast cancer cell migration, invasion, and proliferation.
Appendix
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Metadata
Title
Type I gamma phosphatidylinositol phosphate kinase modulates invasion and proliferation and its expression correlates with poor prognosis in breast cancer
Authors
Yue Sun
Dmitry A Turbin
Kun Ling
Narendra Thapa
Samuel Leung
David G Huntsman
Richard A Anderson
Publication date
01-02-2010
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2010
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2471

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