Post-transcriptional control of c-erb B-2 overexpression in stomach cancer cells.
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.
Bae
C D
CD
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Kyungkido, Korea.
Juhnn
Y S
YS
Park
J B
JB
D020121:5' Untranslated Regions; D001483:Base Sequence; D015972:Gene Expression Regulation, Neoplastic; D006207:Half-Life; D006801:Humans; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D020121:5' Untranslated Regions; D018719:Erb-b2 Receptor Tyrosine Kinases