Raf-1 activation in gastrointestinal carcinoid cells decreases tumor cell adhesion.
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, beta-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 beta-catenin. Raf-1 activation led to decreased expression of beta-catenin.


CONCLUSIONS
Raf-1 induction in carcinoid cells results in a significant decrease in adhesion. Furthermore, the important adhesion regulator, beta-catenin, is decreased in activated BON-raf cells. These Raf-1-related changes in adhesion may alter the metastatic phenotype of carcinoid cells.
Greenblatt
David Yü
DY
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.
Kunnimalaiyaan
Muthusamy
M
Chen
Herbert
H
D002276:Carcinoid Tumor / Q000201:enzymology* / Q000473:pathology* / Q000556:secondary; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005770:Gastrointestinal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D051176:beta Catenin; D019908:Proto-Oncogene Proteins c-raf