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Overexpression of glutamine synthetase in human primary liver cancer.

Abstract：

BACKGROUND/AIMS:We have identified several clones specifically expressed during malignant cell proliferation by screening a complementary DNA library constructed from a human primary liver cancer with subtractive probes. One clone was identified as the glutamine synthetase (GS) transcript. Its expression is tightly regulated during development, especially in the hepatic lobule. Because this enzyme is involved in nitrogen homeostasis, it might contribute to tumor development/progression in primary liver cancer. METHODS:We compared the expression of GS messenger RNA (mRNA) and protein in tumorous and nontumorous liver from 34 patients with primary liver cancers, using a combination of Northern blot, dot blot, western blot, and determination of GS enzyme activity. RESULTS:GS mRNA was higher in tumors versus nontumors in 23 of 34 primary liver cancer samples. GS activity was higher in 6 of 8 selected primary liver cancer samples with high RNA levels. GS protein levels were proportional to enzyme activity. A major GS transcript of 2.8 kilobase was detected by Northern blotting and sequencing. This comprised the minor 1.8-kb transcript and a long 3' untranslated region; the latter contained an AT-rich zone, fully conserved in the chicken, mouse, and rat, which might be important for stability. CONCLUSIONS:Our results show an overexpression of GS in human primary liver cancers and, thus, point to its potential involvement in hepatocyte transformation.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Christa L,Simon MT,Flinois JP,Gebhardt R,Brechot C,Lasserre C

doi

10.1016/0016-5085(94)90024-8

subject

Has Abstract

pub_date

1994-05-01 00:00:00

pages

1312-20

issue

5

eissn

0016-5085

issn

1528-0012

pii

0016-5085(94)90024-8

journal_volume

106

pub_type

杂志文章

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