Abstract. The synucleins (·-, ß-and Á-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 Á-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 ·-or ß-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 · or Á-synuclein expression, as well as positive either for ß or Á-synuclein in more ratios of lymph node-positive tumors. These results show that ·-, ß-and Á-synuclein are expressed in a high percentage of CRC. Á-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 Á-synuclein protein combined with either ·-or ß-synuclein protein or both than by detection of Á-synuclein only.
IntroductionThe synucleins are a family of small, soluble, highly conserved neuronal proteins that consist of ·-, ß-, and Á-synuclein. They are a natively unfolded group of proteins that are characterized by 5-6 repeats of amino acid motif (KTKEGV), constituting most of the N-terminal half of the proteins. These repeats result in the formation of conserved amphipathic A2-helices also characteristic of apolipoproteins, which mediate reversible binding to phospholipid membranes. This property supports the role of synucleins in vesicular release at presynaptic nerve terminals (1-4). Although their normal cellular functions have not been clearly defined, synucleins have attracted considerable attention due to their involvement in neurodegenerative diseases. ·-synuclein is the major component of Lewy bodies in Parkinson's disease and has also been identified as the non-amyloid component of amyloid deposition, the hallmark of Alzheimer's disease (5,6). ß-and Á-synuclein are assumed to have a neuroprotective role by inhibiting ·-synuclein aggregation and toxicity (7,8).Synuclein expression is usually highly tissue-specific, and restricted to brain tissue and presynaptic terminals. However, a...