Detection of lower levels of SNAP25 using multiple microarray systems and its functional significance in medulloblastoma.
Medulloblastoma (MB) is the most common pediatric malignant brain tumor and patients with high-risk or recurrent MB respond poorly to current therapies, and have a higher related mortality. For this reason, potential molecules related to MB need be identified in order to develop targets for the development of novel therapeutics. In the present study, we compared MB microarray data obtained using different microarray systems and significant targets were selected by gene annotation and enrichment analysis. Genes for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) annotated with the function 'vesicle' were identified and one of these proteins, synaptosomal-associated protein 25 (SNAP25), was found to have significantly lower expression levels in MB. In addition, SNAP25 was detected in a very low number of MB cells as shown by western blot analysis and immunohistochemical analyses of archived and formalin-fixed/paraffin-embedded human MB specimens. We found that SNAP25 altered the morphology and the chemotherapeutic effects of arabinofuranosyl cytidine (Ara-C) on SNAP25-expressing MB cells. On the whole, our data indicate that the expression of SNAP25 is crucial for dendrite formation and is associated with the effects of targeted chemotherapy. The detection of SNAP25 expression in MB cells may thus be essential for the chemotherapeutic application of Ara-C.
Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan, R.O.C.
Chi-Jung
CJ
Huang
School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
Chia-Long
CL
Lee
Department of Pathology, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C.
Chih-Yi
CY
Liu
Department of Pathology, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.
Shih-Hung
SH
Huang
Department of Pediatrics, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.
Jia-Woei
JW
Hou
Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.
Yi-Hou
YH
Chen
Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.
Chih-Cheng
CC
Chien
Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.
Chih-Ming
CM
Ho
School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
Wen-Cheng
WC
Lo
Department of Pediatrics, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.
Kun-Long
KL
Hung
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002648:Child; D003561:Cytarabine / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008527:Medulloblastoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D050600:SNARE Proteins; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D059467:Transcriptome; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D050600:SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D003561:Cytarabine