Stem cell factor-mediated wild-type KIT receptor activation is critical for gastrointestinal stromal tumor cell growth  

作　　者：Chen-Guang Bai Xiao-Wei Hou Feng Wang Cen Qiu Yan Zhu Ling Huang Jing Zhao Jing-Jing Xu, Da-Lie Ma 

机构地区：[1]Department of Pathology, Changhai Hospital, Second Mili- tary Medical University, Shanghai 200433, China [2]Institute of Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China [3]Laboratory of Mo- lecular Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China

出　　处：《World Journal of Gastroenterology》2012年第23期2929-2937,共9页世界胃肠病学杂志（英文版）

基　　金：Supported by The National Natural Science Foundation of China, No.30700809 and No.30972876

摘　　要：AIM: To clarify the biological role of stem cell factor (SCF)-mediated wild-type KIT receptor activation in gastrointestinal stromal tumor (GIST) growth. METHODS: The co-expression of wild-type KIT receptor and SCF was evaluated in 51 GIST samples using mutation analysis and immunohistochemistry, and the results were correlated with clinicopathological param- eters, including the mitotic count, proliferative index (Ki-67 immunohistochemical staining), mitotic index (phospho-histone H3 immunohistochemical staining) and apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Using primary cultured GIST cells, the effect of SCF-mediated wild-type KIT receptor activation was determined by western blotting, methyl thiazolyl tetrazolium (MTT), and apoptosis assays. RESULTS: We found that wild-type KIT receptor and SCF protein were expressed in 100% and 76.5% of the 51 GIST samples, respectively, and the co-expression of wild-type KIT receptor and SCF was associated with known indicators of poor prognosis, including larger tumor size (P = 0.0118), higher mitotic count (P = 0.0058), higher proliferative index (P = 0.0012), higher mitotic index (P = 0.0282), lower apoptosis index (P = 0.0484), and increased National Institutes of Health risk level (P = 0.0012). We also found that the introduction of exogenous SCF potently increased KIT kinase activity, stimulated cell proliferation (P < 0.01) and inhibited apoptosis (P < 0.01) induced by serum starvation, while a KIT immunoblocking antibody suppressed proliferation (P = 0.01) and promoted apoptosis (P < 0.01) in cultured GIST cells. CONCLUSION: SCF-mediated wild-type KIT receptor activation plays an important role in GIST cell growth. The inhibition of SCF-mediated wild-type KIT receptor activation may prove to be particularly important for GIST therapy.AIM： To clarify the biological role of stem cell factor （SCF）-mediated wild-type KIT receptor activation in gastrointestinal stromal tumor （GIST） growth. METHODS： The co-expression of wild-type KIT receptor and SCF was evaluated in 51 GIST samples using mutation analysis and immunohistochemistry, and the results were correlated with clinicopathological param- eters, including the mitotic count, proliferative index （Ki-67 immunohistochemical staining）, mitotic index （phospho-histone H3 immunohistochemical staining） and apoptotic index （terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling）. Using primary cultured GIST cells, the effect of SCF-mediated wild-type KIT receptor activation was determined by western blotting, methyl thiazolyl tetrazolium （MTT）, and apoptosis assays. RESULTS： We found that wild-type KIT receptor and SCF protein were expressed in 100% and 76.5% of the 51 GIST samples, respectively, and the co-expression of wild-type KIT receptor and SCF was associated with known indicators of poor prognosis, including larger tumor size （P = 0.0118）, higher mitotic count （P = 0.0058）, higher proliferative index （P = 0.0012）, higher mitotic index （P = 0.0282）, lower apoptosis index （P = 0.0484）, and increased National Institutes of Health risk level （P = 0.0012）. We also found that the introduction of exogenous SCF potently increased KIT kinase activity, stimulated cell proliferation （P 〈 0.01） and inhibited apoptosis （P 〈 0.01） induced by serum starvation, while a KIT immunoblocking antibody suppressed proliferation （P = 0.01） and promoted apoptosis （P 〈 0.01） in cultured GIST cells. CONCLUSION： SCF-mediated wild-type KIT receptor activation plays an important role in GIST cell growth. The inhibition of SCF-mediated wild-type KIT receptor activation may prove to be particularly important for GIST therapy.

关 键 词：Gastrointestinal stromal tumor Stem cellfactor Wild-type KIT receptor Cell growth In vitro 

分 类 号：Q26[生物学—细胞生物学] Q943.1