RRC ID 64981
Author Hou S, Isaji T, Hang Q, Im S, Fukuda T, Gu J.
Title Distinct effects of β1 integrin on cell proliferation and cellular signaling in MDA-MB-231 breast cancer cells.
Journal Sci Rep
Abstract An aberrant expression of integrin β1 has been implicated in breast cancer progression. Here, we compared the cell behaviors of wild-type (WT), β1 gene deleted (KO), and β1 gene restored (Res) MDA-MB-231 cells. Surprisingly, the expression of β1 exhibited opposite effects on cell proliferation. These effects were dependent on cell densities, and they showed an up-regulation of cell proliferation when cells were cultured under sparse conditions, and a down-regulation of cell growth under dense conditions. By comparison with WT cells, the phosphorylation levels of ERK in KO cells were consistently suppressed under sparse culture conditions, but consistently up-regulated under dense culture conditions. The phosphorylation levels of EGFR were increased in the KO cells. By contrast, the phosphorylation levels of AKT were decreased in the KO cells. The abilities for both colony and tumor formation were significantly suppressed in the KO cells, suggesting that β1 plays an important role in cell survival signaling for tumorigenesis. These aberrant phenotypes in the KO cells were rescued in the Res cells. Taken together, these results clearly showed the distinct roles of β1 in cancer cells: the inhibition of cell growth and the promotion of cell survival, which may shed light on cancer therapies.
Volume 6
Pages 18430
Published 2016-1-5
DOI 10.1038/srep18430
PII srep18430
PMID 26728650
PMC PMC4700444
MeSH Breast Neoplasms / genetics Breast Neoplasms / metabolism* Breast Neoplasms / pathology Cell Adhesion / genetics Cell Line, Tumor Cell Movement / genetics Cell Proliferation / drug effects Cell Transformation, Neoplastic / genetics ErbB Receptors / antagonists & inhibitors ErbB Receptors / metabolism Female Gene Deletion Gene Expression Gene Knockout Techniques Humans Integrin beta1 / chemistry Integrin beta1 / genetics Integrin beta1 / metabolism* Protein Kinase Inhibitors Protein Subunits / genetics Quinazolines / pharmacology Signal Transduction* Tyrphostins / pharmacology
IF 3.998
Human and Animal Cells 293T(RCB2202)