Post-transcriptional control of c-erb B-2 overexpression in stomach cancer cells.
- Author:
Chang Dae BAE
1
;
Yong Sung JUHNN
;
Joo Bae PARK
Author Information
1. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Kyungkido, Korea.
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
c- erb B-2;
oncogene;
overexpression;
stomach cancer
- MeSH:
5' Untranslated Regions;
Base Sequence;
Comparative Study;
Gene Expression Regulation, Neoplastic;
Half-Life;
Human;
Molecular Sequence Data;
Protein Processing, Post-Translational;
Receptor, erbB-2/*genetics/*metabolism;
Stomach Neoplasms/genetics/*metabolism;
Support, Non-U.S. Gov't;
Transcription, Genetic;
Tumor Cells, Cultured
- From:Experimental & Molecular Medicine
2001;33(1):15-19
- CountryRepublic of Korea
- Language:English
-
Abstract:
The growth factor receptor oncogene, c-erb B-2, is frequently overexpressed in the adenocarcinomas of breast, ovary, lung and stomach. Although the mechanism of erb B-2 overexpression is thought as the result of transcriptional upregulation in many primary human carcinomas, expression rate of c-erb B-2 at mRNA level is usually lower than the level of translated protein. We also found that the expression of erb B-2 in SNU-1 stomach cancer cells was greater at post-transcription level (Bae et al., 1993). To explore the underlying mechanism of erb B-2 protein overexpression, we have chosen two cells lines, SNU-1 and SNU-16 where transcription rate of erb B-2 was closely resemble to each other while expressed protein levels were quite different. The synthesis rate of erb B-2 protein in SNU-1 cells was faster than SNU-16 cells while levels of erb B-2 mRNA were found to be similar in both cell lines. The half-life of the expressed erb B-2 protein was not significantly different in both cell lines. Analysis of the 5' untranslated region (UTR) of erb B-2 mRNA (-1approximately-323) showed no sequence abnormality in both cell lines. However, ribonuclease protection assay using cloned 5 UTR sequence revealed that the size of 5' UTR of erb B-2 mRNA which associate with transcription initiation site(s) in SNU-1 cells was longer than that in SNU-16. These results suggest that the increased erb B-2 protein synthesis rate possibly due to the redundant selection of transcription initiation might be a mechanism of erb B-2 overexpression in SNU-1 cells.