Raf-1 activation in gastrointestinal carcinoid cells decreases tumor cell adhesion
Presented at the 49th Annual Meeting of the Midwest Surgical Society, Mackinac Island, MI, August 6–9, 2006
Received 12 August 2006; received in revised form 20 September 2006
Abstract
Background
Gastrointestinal carcinoid tumors are highly metastatic. Activation of the Raf-1 signaling pathway in carcinoid cells results in morphologic changes. These Raf-1–induced structural changes may affect cellular adhesion, thereby altering metastatic potential.
Methods
An estrogen-inducible Raf-1 cell line (BON-raf) was used to study the effects of Raf-1 on cellular adhesion. Cell adhesion was measured before and after Raf-1 induction. Western blot analysis was used to confirm Raf-1 activation and measure levels of an essential adhesion regulator, β-catenin.
Results
Estrogen treatment of BON-raf cells resulted in Raf-1 activation and a marked decrease (68%) in cell adhesion. In the absence of Raf-1 induction, carcinoid cells expressed high levels of β-catenin. Raf-1 activation led to decreased expression of β-catenin.
Conclusions
Raf-1 induction in carcinoid cells results in a significant decrease in adhesion. Furthermore, the important adhesion regulator, β-catenin, is decreased in activated BON-raf cells. These Raf-1-related changes in adhesion may alter the metastatic phenotype of carcinoid cells.
Endocrine Surgery Research Laboratories, Section of Endocrine Surgery, Department of Surgery, University of Wisconsin, H4/750 Clinical Science Center, 600 Highland Ave., Madison, WI 53792, USA
ABSTRACT