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Endocrinology, Vol 132, 1145-1150, Copyright © 1993 by Endocrine Society

ARTICLES

Differential promoter activation in two human insulin-like growth factor-II-producing tumor cell lines

H Schneid, PE Holthuizen and JS Sussenbach
Institut National de la Sante et de la Recherche Medicale, Unite 142 (H.S.), Hopital Saint Antoine, Paris, France.

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.


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