Overexpression of synuclein-gamma in pancreatic adenocarcinoma.
BACKGROUND
Currently, pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Despite the advances in pancreatic carcinoma research, patients with this devastating disease have a very poor prognosis. To identify the gene expression profile of pancreatic carcinoma, an important step in the process of developing new diagnostic and therapeutic strategies, the authors investigated the alteration of gene expression in this disease.


METHODS
The authors analyzed a public serial analysis of gene expression (SAGE) database and examined in greater detail the expression of synuclein-gamma mRNA in several pancreatic carcinoma cell lines and tumor tissue samples by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and Northern blot analysis. The expression of synuclein-gamma protein was investigated further by immunohistochemical and Western blot analyses using tumor cell lines, tumor tissue, and serum samples.


RESULTS
Synuclein-gamma mRNA was overexpressed in 11 of 12 pancreatic carcinoma cell lines, including AsPc-1, MDAPanc28, Capan-1, Capan-2, PANC-1, HS766T, MDAPanc3, MDAPanc48, Colo357FG, MiaPaCa2, CFPac1, and BxPc3. The expression of synuclein-gamma protein was detectable in 8 of 12 pancreatic carcinoma cell lines (67%) and in 22 of 32 pancreatic tumor tissue samples (69%) by Western blot analysis. On immunohistochemical staining, synuclein-gamma protein was present in 61% of the tumor tissue samples examined from patients with Stage I and II pancreatic carcinoma. The overexpression of synuclein-gamma is correlated with perineural and lymph node invasion. Synuclein-gamma protein also was detectable by Western blot in serum samples from 21 of 56 patients (38%) with pancreatic carcinoma.


CONCLUSIONS
Synuclein-gamma, which initially was described as a breast carcinoma-specific gene involved in invasion, metastasis, and chemotherapy resistance, was frequently overexpressed in pancreatic carcinoma. Overexpression of synuclein-gamma may play a role in pancreatic carcinoma invasion. Further studies will be necessary to determine the role of synuclein-gamma in pancreatic carcinoma.
Li
Zhongkui
Z
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, PO Box 424, Houston, TX 77030, USA.
Sclabas
Guido M
GM
Peng
Bailu
B
Hess
Kenneth R
KR
Abbruzzese
James L
JL
Evans
Douglas B
DB
Chiao
Paul J
PJ
D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000097:blood; D010190:Pancreatic Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051843:Synucleins
D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; D051843:Synucleins