ERBB-2 overexpression confers PI 3 kinase-dependent invasion capacity on human mammary epithelial cells

Amplification and overexpression of ERBB-2 in human breast cancer is thought to play a significant role in the progression of the disease; however, its precise role in the aetiology of altered phenotypes associated with human breast cancer is unknown. We have previously shown that exogenous overexpr...

Full description

Saved in:
Bibliographic Details
Published in:British journal of cancer 2000-02, Vol.82 (3), p.666-674
Main Authors: Ignatoski, K M Woods, Maehama, T, Markwart, S M, Dixon, J E, Livant, D L, Ethier, S P
Format: Article
Language:English
Subjects:
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Breast - cytology
Breast - enzymology
Breast - metabolism
Breast cancer
Breast Neoplasms - enzymology
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer Research
Cell Division
Cell Survival
Drug Resistance
Epidemiology
erbB-2 gene
FAK protein
Gene amplification
Genes, erbB-2
Growth factors
Gynecology. Andrology. Obstetrics
Humans
Kinases
Mammary gland diseases
Medical sciences
Molecular Medicine
Neoplasm Invasiveness - genetics
Oncology
Phenotype
Phosphatidylinositol 3-Kinases - metabolism
PTEN gene
Regular
regular-article
Signal Transduction
Tumors
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Amplification and overexpression of ERBB-2 in human breast cancer is thought to play a significant role in the progression of the disease; however, its precise role in the aetiology of altered phenotypes associated with human breast cancer is unknown. We have previously shown that exogenous overexpression of ERBB-2 conferred growth factor independence on human mammary epithelial cells. In this study, we show that ERBB-2 overexpression also causes the cells to acquire other characteristics exhibited by human breast cancer cells, such as anchorage-independent growth and invasion capabilities. ERBB-2-induced invasion is dependent on fibronectin and correlates with the down-regulation of cell surface α4 integrin. In addition ERBB-2 co-immunoprecipitates with focal adhesion kinase (FAK) in these cells. We have also shown, by use of exogenously expressed PTEN and by treatment with the PI3′-kinase inhibitor LY294002, that ERBB-2-induced invasion is dependent on the PI3′-kinase pathway; however, PTEN does not dephosphorylate FAK in these cells. © 2000 Cancer Research Campaign
ISSN:0007-0920
1532-1827
DOI:10.1054/bjoc.1999.0979