Oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor / 中华胃肠外科杂志
Chinese Journal of Gastrointestinal Surgery
; (12): 371-374, 2010.
Article
在 Zh
| WPRIM
| ID: wpr-266338
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To characterize oncogenic KIT signaling mechanisms in gastrointestinal stromal tumor(GIST), and to determine which signaling pathway might be of potential relevance to imatinib acquired resistance.</p><p><b>METHODS</b>The mutations of KIT and PDGFRa gene were evaluated and KIT downstream signaling profiles were evaluated in 8 specimen from 5 GIST patients who were evaluated treated between 2003 and 2008 in our hospital. Biochemical inhibition of the expression of related proteins in Ras/Raf/MAPK and PI3-K/AKT pathways, such as KIT, mitogen-activated protein kinase(MAPK),mammalian target of rapamycin(MTOR), AKT, Proliferating cell nuclear antigen (PCNA) and BCL-2, were determined by Western blotting for protein activation.</p><p><b>RESULTS</b>Three cases who showed response to imatinib carried primary mutations in KIT gene, with 2 cases possessing mutation in exon 11, 1 case in exon 13. One case with imatinib-resistance developed KIT secondary mutation, but all the cases had no PDGFRa mutation. p-KIT and p-AKT expressions were higher in the samples of imatinib-resistant GIST than those of imatinib-responsive GIST. Total KIT, MAPK, p-MAPK, p-MTOR expressions were strong and comparable in all varied GISTs, which had no significant difference between imatinib-resistant and imatinib-responsive samples. PCNA and BCL-2 expression varied in samples of different therapy cycles and different location.</p><p><b>CONCLUSIONS</b>Ras/Raf/MAPK and PI3-K/AKT/MTOR pathways are essential to GIST pathogenesis. The KIT secondary mutation and PI3-K/AKT/MTOR pathway are particularly relevant for therapeutic targeting in imatinib-resistant GIST.</p>
全文:
1
索引:
WPRIM
主要主题:
Pharmacology
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Piperazines
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Pyrimidines
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Benzamides
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Signal Transduction
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Proto-Oncogene Proteins c-kit
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Drug Resistance, Neoplasm
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Gastrointestinal Stromal Tumors
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Drug Therapy
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Imatinib Mesylate
限制:
Humans
语言:
Zh
期刊:
Chinese Journal of Gastrointestinal Surgery
年:
2010
类型:
Article