Cholinesterases are down-expressed in human colorectal carcinoma

Abstract

The aberrations of cholinesterase (ChE) genes and the variation of ChE activity in cancerous tissues prompted us to investigate the expression of ChEs in colorectal carcinoma. The study of 55 paired specimens of healthy (HG) and cancerous gut (CG) showed that acetylcholinesterase (AChE) activity fell by 32% and butyrylcholinesterase (BuChE) activity by 58% in CG. Abundant AChE-H, fewer AChE-T, and even fewer AChE-R and BuChE mRNAs were observed in HG, and their content was greatly diminished in CG. The high level of the AChE-H mRNA explains the abundance of AChE-H subunits in HG, which as glycosylphosphatidylinositol (GPI)-anchored amphiphilic AChE dimers (G2(A)) and monomers (G1(A)) account for 69% of AChE activity. The identification of AChE-T and BuChE mRNAs justifies the occurrence in gut of A12, G4(H) and PRiMA-containing G4(A) AChE forms, besides G4(H), G4(A) and G1(H) BuChE. The down-regulation of ChEs might contribute to gut carcinogenesis by increasing acetylcholine availability and over-stimulating muscarinic receptors.

Acetylcholinesterase in intestinal cell differentiation involves G2/M cell cycle arrest

“…AChE upregulation was also observed correlated with the differentiation state of osteoblasts and staurosporine-treated human prostate cancer cells [48,49]. Expression of AChE in cancers of the colon, sigmoid colon, and in rectal cancers was found to be reduced compared to normal tissues [50,51]. However, to date no studies have addressed the role of AChE in the transformation of colon epithelial cells.…”

Acetylcholinesterase is associated with a decrease in cell proliferation of hepatocellular carcinoma cells

“…This seems to be the case for metastasized lymph node as the result of breast cancer [31], as well as for colon cancer [32], and some lung tumor types [33]. However, the relation of low AChE activity with malignancy is not so obvious reminding the enhanced AChE activity observed in some thymoma classes [34] and renal cell carcinoma types [11], which in turn highlights how complex the variation of AChE expression can be in cancerous tissues.…”

Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect

“…The lymphocytes from CLL patients showed significantly lower AChE activity than normal [20]. In comparsion of 55 paired tissues of healthy and cancerous gut, 32% decrease of AChE activity was observed in cancerous gut [21]. Increased ACh was found in lung cancer tissues due to the abnormal expression of AChE [22].…”