Ruginis Tom, Taglia Lauren, Matusiak Damien, Lee Bao-Shiang, Benya Richard V
Department of Medicine, University of Illinois at Chicago and Chicago Veterans Administration Medical Center (West Side Division), Chicago, Illinois 60612, USA.
J Proteome Res. 2006 Jun;5(6):1460-8. doi: 10.1021/pr060005g.
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.
胃泌素释放肽（GRP）及其受体（GRPR）在结肠癌中异常上调。当它们表达时，会作为形态发生素发挥作用，使肿瘤细胞保持在分化更好的状态并延缓转移。为了鉴定响应GRPR信号激活的靶点，我们研究了Caco-2和HT-29细胞，这两种结肠癌细胞系会根据汇合度表达GRPR。从在无血清培养基中培养的未汇合细胞（表达GRP/GRPR）中提取总细胞蛋白，这些细胞处于存在或不存在GRPR特异性拮抗剂的条件下；同时也从未表达GRPR的汇合细胞中提取。总体而言，我们鉴定出5种在GRP/GRPR表达后特异性下调的蛋白质：Bach2、肌酸激酶B、p47以及两种无法鉴定的蛋白质；还有6种上调的蛋白质：gephyrin、HSP70、HP1、ICAM-1、ACAT以及一种无法鉴定的蛋白质。这些发现表明，GRP/GRPR在结肠癌中介导其形态发生作用的机制涉及许多迄今未被重视的蛋白质的作用。
