Journal
SURGERY
Volume 136, Issue 2, Pages 143-149Publisher
MOSBY, INC
DOI: 10.1016/j.surg.2004.04.006
Keywords
-
Categories
Funding
- NCI NIH HHS [R01 CA104748] Funding Source: Medline
- NIA NIH HHS [2R37 AG10885] Funding Source: Medline
- NIDDK NIH HHS [T32 DK07639, P01 DK35608, R01 DK48489] Funding Source: Medline
Ask authors/readers for more resources
Background. Phosphatidylinositol 3-kinase (PI3K), acting through the downstream kinase AKT, regulates a number of cellular processes such as cell growth and survival. Poorly differentiated colon cancers are characterized by increased integrin-mediated extracellular mat-fix interactions; disruption of this integrin-mediated adhesion leads to apoptosis and involves reduced PI3K activity. The purpose of this study was to determine: (1) the role of alpha5beta1 integrin expression on PI3K activity, and (2) whether blockade of alpha5beta1 integrin decreases colon cancer cell adhesion and increases apoptosis. Methods. Human colon cancer cells were treated with anti-alpha5 integrin antibody, anti-beta1 integrin antibody, the PI3K inhibitor LY294002 (20 mumol/L), or wortmannin (400 nmol/L). Expression and function of alpha5 were quantitated by FACS analysis and cell adhesion assay, respectively. DNA. fragmentation was measured to assess apoptosis. Protein was extracted to determine phosphorylated AKT (pAKT) expression as a measure of PI3K activity. Results. Increased pAKT and a5 integrin expression were noted in the colon cancer cells; blockade of a5 integrin decreased alpha5 integrin and pAKT expression and decreased cell adhesion. Moreover, PI3K inhibition resulted in decreased a5 integrin expression. In contrast, treatment with anti-beta1 integrin antibody produced no change in pAKT expression or cell number. Conclusion. Our results are the first to show that blockade of cell surface alpha5 integrin expression decreases PI3K activity, inhibits colon cancer cell attachment, and induces apoptosis. These findings suggest that agents which selectively target alpha5 integrin subunit expression may enhance the effects of standard chemotherapeutic agents and provide novel adjuvant treatment for selected colon cancers.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available