Differential promoter activation in two human insulin-like growth factor-II-producing tumor cell lines.
Several lines of evidence suggest that the growth factor insulin-like growth factor-II (IGF-II) is involved in the genesis of several types of tumors and may have autocrine effects on tumor progression when overexpressed. The human IGF-II gene is a complex transcription unit. Multiple transcripts are synthesized as a result of alternate promoter usage and the splicing of unique 5'-untranslated regions to common coding exons. We have examined two human tumor cell lines that both produce IGF-II protein which can function as an autocrine growth factor. Interestingly, each cell line uses a different IGF-II promoter; Hep3B cells predominantly activate P3, whereas in SW613 cells P4 is the preferred promoter. Here, we examine the differential transcriptional activation of the human IGF-II gene in Hep3B and SW613 cells by means of transient transfection assays and electrophoretic mobility shift analysis. The results indicate that production of IGF-II protein is mainly regulated at the level of transcription. Additional regulation takes place at the levels of messenger RNA stability and efficiency of translation.
Schneid
H
H
Institut National de la Santé et de la Recherche Médicale, Unité 142 (H.S.), Hôpital Saint Antoine, Paris, France.
Holthuizen
P E
PE
Sussenbach
J S
JS
D006528:Carcinoma, Hepatocellular; D002467:Cell Nucleus / Q000378:metabolism; D003110:Colonic Neoplasms; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D008113:Liver Neoplasms; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II