Gnatt_1990_Cancer.Res_50_1983

Reference

Title : Expression of alternatively terminated unusual human butyrylcholinesterase messenger RNA transcripts, mapping to chromosome 3q26-ter, in nervous system tumors - Gnatt_1990_Cancer.Res_50_1983
Author(s) : Gnatt A , Prody CA , Zamir R , Lieman-Hurwitz J , Zakut H , Soreq H
Ref : Cancer Research , 50 :1983 , 1990
Abstract : To study the molecular origin of the altered regulation of butyrylcholinesterase (BCHE) in nervous system tumors, BCHE complementary DNA (cDNA) sequences from human glioblastoma and neuroblastoma cDNA libraries were compared with BCHE cDNAs from normal fetal and adult tissues. A single 2.6-kilobase BCHE cDNA sequence was found in all normal tissues, whereas an additional alternatively terminated BCHE cDNA clone was found in both tumor libraries. The tumor-specific cDNA contained a 3',0.7-kilobase nontranslatable extension, as well as several nucleotide alterations in the normal polyadenylation site. Single-base mutations in the coding region of this unusual BCHE cDNA infer two amino acid substitutions: Asp70----Gly and Ser425----Pro. The Asp70----Gly change has recently been implicated with "atypical" BCHE, which is deficient in its capacity to hydrolyze succinylcholine. The 3.6-kilobase mRNA was less abundant in RNA blot hybridization than the 2.6-kilobase mRNA, which is in agreement with the low ratios between the 3.6- and 2.6-kilobase BCHE cDNA clones in glioblastoma and neuroblastoma libraries. Furthermore, size fractionation and microinjection of glioblastoma polyadenylated RNA, followed by enzyme activity and selective inhibition measurements, demonstrated two peaks of functional BCHE mRNA, the heavier one probably reflecting the longer transcripts. Chromosomal mapping of the 0.7-kilobase 3' fragment by in situ hybridization localized it to a unique 3q26-ter position, where we recently found an inheritably amplified "silent" defective CHE gene in a family exposed to the cholinesterase inhibitor methyl parathion. Our findings confirm previous genetic linkage mapping of the functional CHE gene to the 3q26-ter position and demonstrate that extended functional mRNA transcripts encoding a BCHE form with two modified amino acids are produced from this gene in glioblastoma and neuroblastoma cells.
ESTHER : Gnatt_1990_Cancer.Res_50_1983
PubMedSearch : Gnatt_1990_Cancer.Res_50_1983
PubMedID: 2317787

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Gnatt A, Prody CA, Zamir R, Lieman-Hurwitz J, Zakut H, Soreq H (1990)
Expression of alternatively terminated unusual human butyrylcholinesterase messenger RNA transcripts, mapping to chromosome 3q26-ter, in nervous system tumors
Cancer Research 50 :1983

Gnatt A, Prody CA, Zamir R, Lieman-Hurwitz J, Zakut H, Soreq H (1990)
Cancer Research 50 :1983