Acetylcholinesterase and butyrylcholinesterase genes coamplify in primary ovarian carcinomas.

Abstract

The genes for acetylcholinesterase (ACHE) and butyrylcholinesterase (CHE) are expressed in multiple tumor tissues, including ovarian carcinomas. Both CHE and ACHE genes coamplify in leukemias. To examine the relationship of gene amplification to the expression of these genes in tumors, ACHE and CHE genes and their expression were studied in primary ovarian carcinomas. DNA blot hybridization demonstrated a significant amplification and mutagenesis of both genes in 6 of 11 malignant tumors studied. This was greater or of the same order of magnitude as the amplification of the oncogenes c-rafi, v-sis, and c-fes in these tumors. No amplification was found in normal ovarian tissues or benign ovarian cysts. Xenopus oocyte microinjections, blot and in situ hybridizations, and immuno-and cytochemical staining revealed translatable CHEmRNA and its active protein product in discrete tumor foci. The frequent coamplification in ovarian carcinomas of ACHE and CHE genes implicates cholinesterases in neoplastic growth and/or proliferation. (J. Clin. Invest. 1990. 86:900-908.)

Expression of a human acetylcholinesterase promoter-reporter construct in developing neuromuscular junctions of Xenopus embryos.

“…Its sequence further predicts responses to cAMP-inducing stimuli and signal transduction pathways in nervous system cell lineages as well as control by additional distant enhancer sequences, in good agreement with the multiplicity of human tissues and developmental stages where the AcChoEase protein has been observed (6). Furthermore, binding sites for early/immediate gene products (i.e., E-Box and Egrl) may explain AcChoEase expression in tumor tissues and may relate to the tumorigenic amplification of this gene (27,28). The existence of an NF-KB element within the first intron could possibly imply that expression of the ACHE gene in lymphocytes is subject to regulation by transcription factors binding this intron and affecting cell cycle-related control, limited to the Go-G1 transition phase (16).…”

Cholinesterase activity as biomarker of neurotoxicity: utility in the assessment of aquatic environment contamination

“…In embryonic life, definition of the role of cholinesterases in cellular proliferation and differentiation have started the investigations on possible involvement of BChE and AChE in tumorogenesis. Abnormal expression of both BChE and AChE, and in vivo amplification of their genes have been observed in intracranial neoplasms such as meningioma (67), glioma (68), and acuostic neurinomas (69), lung cancers (70), megakaryocytopoietic disorders and leukemias (71), ovarian tumors (72). It is also shown that AChE and BChE modulate cell adhesion in human neuroblastoma cells (62).…”

Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure.

“…1A). Since tightly folded G+C-rich DNA sequences display distinct replication patterns during the cell cycle (27), we wished to examine whether this sequence domain is faithfully replicated in vivo, particularly in cases where AcChoEase gene amplification occurs (5,7). For this purpose, DNA hybridization was performed using 5' and 3' regional probes: (i) an Sph I fragment including the putative attenuator sequence, derived from the 5' GNACHE clone, and (ii) the 3' NBG8A probe, similar to the 1.5-kb fragment that was previously used to detect the AcChoEase gene amplification phenomenon (5, 7).…”

“…LA); its restriction pattern should resemble that of the native AcChoEase gene. DNA was transferred to GeneScreen (DuPont/ NEN) and hybridized with the 32P-labeled 5' and 3' probes as detailed (5 similarly digested transferred plasmid DNA including the AcChoEase genomic DNA insert was employed as a control for the genomic blots ( Fig. 3B; refs.…”

“…AcChoEase may be distinguished from the closely related enzyme butyrylcholinesterase (BtChoEase; acylcholine acylhydrolase, EC 3.1.1.8) by its high substrate specificity and sensitivity to selective inhibitors (2). Cytochemical and biochemical studies have shown that both enzymes are transiently expressed in hematopoietic (3), embryonic (4), and tumor (5) tissues as well, demonstrating distinct patterns of regulation (6). Recently, the genes encoding AcChoEase and BtChoEase in humans were both found to be amplified in leukemic blood cells (7) and in primary ovarian carcinomas (5), reinforcing the notion that they play a growth-related role(s) (8).…”