KIT expression and methylation in medulloblastoma and PNET cell lines and tumors.
The stem cell factor/kit tyrosine kinase receptor pathway is related to tumor growth and progression in several cancers including Ewing sarcoma, a peripheral PNET (pPNET). Identifying additional groups of tumors that may use the pathway is important as they might be responsive to imatinib mesylate treatment. MB and central PNET (cPNET) are embryonal tumors of the CNS that share similar undifferentiated morphology with Ewing sarcomas and display aggressive clinical behavior. cPNET outcome is significantly lower than MB outcome, even for localized tumors treated with high-risk MB therapy. The elucidation of signaling pathways involved in MB and cPNET pathogenesis, and the discovery of new therapeutic targets is necessary to improve the treatment of these neoplasms. We analyzed KIT expression in 2 MB, one pPNET, one cPNET and 2 rhabdomyosarcoma (RMS) cell lines. Also, in 13 tumor samples (12 MB and one cPNET), we found KIT overexpression in the most aggressive cell lines (metastatic MB and pPNET). Hypermethylation of KIT was clear in the RMS non-expressing cell lines. Among MB tumors, we could see variable levels of KIT expression; a subset of them (25%) might be related in its growth pattern to KIT up-regulation. No methylated KIT was detected in the tumors expressing the lowest levels of KIT. Our results point to methylation as an epigenetic regulatory mechanism for KIT inhibition only in the KIT non-expressing RMS cell lines, and neither in the rest of the cell lines nor in the tumor samples.
Enguita-Germán
Mónica
M
Brain Tumor Biology Unit-CIFA, University of Navarra School of Sciences, Irunlarrea 1, 31008, Pamplona, Spain.
Gurrea
Mikel
M
Schiapparelli
Paula
P
Zhu
Thant S
TS
Crowley
Jessica G
JG
Hamm
Lisa L
LL
Costello
Mark A
MA
He
Xiaobing
X
Talsma
Caroline E
CE
Flack
Callie G
CG
Hervey-Jumper
Shawn L
SL
Heth
Jason A
JA
Muraszko
Karin M
KM
Rey
Juan A
JA
Fan
Xing
X
Castresana
Javier S
JS
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism; D018317:Nerve Sheath Neoplasms / Q000235:genetics* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
D019009:Proto-Oncogene Proteins c-kit