Post-transcriptional control of c-erb B-2 overexpression in stomach cancer cells

• Published in: Experimental & molecular medicine 2001-03, Vol.33 (1), p.15-19
• Main Authors: Bae, C D, Juhnn, Y S, Park, J B
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions; Base Sequence; Gene Expression Regulation, Neoplastic; Half-Life; Humans; Molecular Sequence Data; Protein Processing, Post-Translational; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Transcription, Genetic; Tumor Cells, Cultured
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.1038/emm.2001.3

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.