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Wild-type KIT overexpression in colon cancer : protein kinase C-δ-mediated recycling of KIT

Other Titles
 대장암에서 정상형 KIT 단백질 과발현 : protein kinase C-δ를 통한 KIT recycling 
Authors
 박미선 
Issue Date
2013
Description
Dept. of Medical Science/석사
Abstract
Abnormal signaling through receptor tyrosine kinase (RTK) moieties is important in tumorigenesis and drug targeting of colorectal cancers (CRCs). Wild type KIT (WT-KIT), a RTK that is activated upon binding with stem cell factor (SCF), is highly expressed in some colon cancers; however, little is known about the functional role of SCF-dependent KIT activation in colon cancer pathogenesis. We aimed to elucidate the conditions and roles of WT-KIT activation in colon cancer tumorigenesis. CRCs with KIT expression were characterized by immunoblotting and immunohistochemistry. The biological alterations after KIT-SCF binding were analyzed with or without protein kinase C (PKC) activation. We found that WT-KIT was expressed in a subset of colon cancer cell lines and was activated by SCF, leading to activation of downstream AKT and ERK signaling pathways. We also demonstrated that KIT expression gradually decreased after prolonged SCF stimulation due to lysosomal degradation. Degradation of WT-KIT after SCF binding was significantly rescued when PKC was activated. We also demonstrated the involvement of activated PKC-δ in the recycling of WT-KIT. We further showed that a subset of CRCs exhibit expressions of both WT-KIT and activated PKC-δ and that expression of KIT is correlated with poor patient survival (P=.004). Continuous downstream signal activation after KIT-SCF binding is accomplished through PKC-δ-mediated recycling of KIT. This sustained KIT activation may contribute to tumor progression in a subset of colon cancers with KIT expression, and might provide the rationale for a therapeutic approach targeting KIT.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/134635
Appears in Collections:
2. Thesis / Dissertation (학위논문) > 1. College of Medicine (의과대학) > Master's Degree (석사)
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