title: Expression of stem cell factor in gastrointestinal stromal tumors: Implications for proliferation and imatinib resistance.
abstract: KIT autophosphorylation caused by mutation of KIT is considered to be a critical mechanism for the oncogenesis of gastrointestinal stromal tumors (GISTs). However, little is known regarding whether stem cell factor (SCF), the KIT ligand, is able to induce the proliferation of GIST cells by activating the wild-type KIT receptor in GISTs. Imatinib, a tyrosine kinase inhibitor, has been demonstrated to be effective as treatment for the majority of GISTs. However, primary resistance to imatinib in GISTs with wild-type KIT and acquired resistance in GISTs with mutant KIT are becoming increasingly significant problems. The aims of this study were to detect the expression and function of SCF in 68 GIST samples, and to explore the relationship between SCF activity and imatinib resistance using immunohistochemical staining and western blot analysis. Results showed abundant expression of SCF in GISTs and demonstrated that SCF is capable of enhancing GIST cell proliferation. Similar to its ineffectiveness in wild-type GISTs, imatinib also failed to inhibit SCF-induced KIT activation in GISTs with mutant KIT. We also found increased SCF expression in GIST cells treated with imatinib. Overall, our results indicated that SCF-induced KIT activation is a novel essential pathway for the proliferation of GISTs. Imatinib was not able to inhibit the activity of SCF, while it promoted the expression of SCF, which may have contributed to acquired imatinib resistance.
authors: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433; ; Department of Oncology, 401 Hospital of PLA, Qingdao, Shandong 266071;
authors: Xiao-Wei
authors: XW
authors: Hou
authors: Chen-Guang
authors: CG
authors: Bai
authors: Xiao-Hong
authors: XH
authors: Liu
authors: Cen
authors: C
authors: Qiu
authors: Ling
authors: L
authors: Huang
authors: Jing-Jing
authors: JJ
authors: Xu
authors: DA-Lie
authors: DL
authors: Ma
keywords: KIT; gastrointestinal stromal tumor; imatinib resistance; stem cell factor