Expression of alpha-, beta- and gamma-synuclein in colorectal cancer, and potential clinical significance in progression of the disease.
The synucleins (alpha-, beta- and gamma-synuclein) are a small, soluble, highly conserved group of neuronal proteins that attracted considerable attention due to their involvement in both neurodegenerative diseases and cancer. In this study, we examined the synuclein exprsssion in colorectal cancer (CRC) tissues, tumor-matched non-neoplastic adjacent tissues (NNAT), and CRC cell lines, and then investigated clinical significance of synucleins. By using semi-quantitative RT-PCR, synuclein mRNA expression was detected in eight CRC cell lines. It was much higher in CRC samples than in NNAT samples (P<0.05). The results of western blotting showed that the levels of synucleins protein expression in CRC cells approximately corresponded to the levels of synuclein mRNA expression. Immunohistochemical staining revealed that gamma-synuclein protein expression was up-regulated in CRC samples compared to NNAT samples (P=0.022), and was significantly correlated with clinical stage and lymph node involvement of CRC (P<0.05). Although, there was no significant difference in either alpha- or beta-synuclein protein expression between tumor and normal samples (P>0.05), often more than one form of synuclein was expressed in a tumor sample. More ratios of later stage and lymph node-positive tumors expressed a least one type of synuclein protein, and more ratios showed positive for either alpha or gamma-synuclein expression, as well as positive either for beta or gamma-synuclein in more ratios of lymph node-positive tumors. These results show that alpha-, beta- and gamma-synuclein are expressed in a high percentage of CRC. gamma-synuclein protein is valuable for evaluation of progression of CRC, and it is more sensitive to predict advanced stage and lymph node invasion by detection of gamma-synuclein protein combined with either alpha- or beta-synuclein protein or both than by detection of gamma-synuclein only.
Ye
Qing
Q
Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
Wang
Ting-Feng
TF
Peng
Yuan-Fei
YF
Xie
Jing
J
Feng
Bo
B
Qiu
Ming-Yuan
MY
Li
Liang-Hui
LH
Lu
Ai-Guo
AG
Liu
Bing-Ya
BY
Zheng
Min-Hua
MH
D018938:Caco-2 Cells; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008207:Lymphatic Metastasis; D016555:Matched-Pair Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism; D051846:beta-Synuclein / Q000235:genetics* / Q000378:metabolism; D051845:gamma-Synuclein / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D051844:alpha-Synuclein; D051846:beta-Synuclein; D051845:gamma-Synuclein