Consequence of gastrin-releasing peptide receptor activation in a human colon cancer cell line: a proteomic approach.
Gastrin-releasing peptide (GRP) and its receptor (GRPR) are aberrantly up-regulated in colon cancer. When expressed, they act as morphogens, retaining tumor cells in a better differentiated state and retarding metastasis. To identify targets activated in response to GRPR signaling we studied Caco-2 and HT-29 cells, colon cancer cell lines that expresses GRPR as a function of confluence. Total cell protein was extracted from pre-confluent cells (expressing GRP/GRPR) cultured in serum-free media in the presence or absence of GRPR-specific antagonist; as well as from confluent cells that do not express GRPR. Overall, we identified 5 proteins that are specifically down-regulated after GRP/GRPR expression: Bach2, creatine kinase B, p47, and two that could not be identified; and 6 proteins that are up-regulated: gephyrin, HSP70, HP1, ICAM-1, ACAT, and one that could not be identified. These findings suggest that the mechanism(s) by which GRP/GRPR mediate its morphogenic effects in colon cancer involve the actions of a number of hitherto unappreciated proteins.
Ruginis
Tom
T
Department of Medicine, University of Illinois at Chicago and Chicago Veterans Administration Medical Center (West Side Division), Chicago, Illinois 60612, USA.
Taglia
Lauren
L
Matusiak
Damien
D
Lee
Bao-Shiang
BS
Benya
Richard V
RV
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D016895:Culture Media, Serum-Free; D015180:Electrophoresis, Gel, Two-Dimensional; D019886:Gastrin-Releasing Peptide / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D020543:Proteome / Q000378:metabolism*; D018004:Receptors, Bombesin / Q000819:agonists / Q000096:biosynthesis*; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D016895:Culture Media, Serum-Free; D020543:Proteome; D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide