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Regulation of HMGIC expression: an architectural transcription factor involved in growth control and development

Oncogene volume 18, pages 5076–5087 (1999)Cite this article

Abstract

The HMGIC gene has been implicated in the control of cell proliferation and development. We show here that HMGIC has multiple mRNA isoforms that arise by transcription initiation from alternative tandem promoters. These transcripts are not only differentially expressed between cell lines, but they can also differ within an individual cell line, in response to particular stimuli. Whereas quiescent 3T3-L1 preadipocytes express low levels of HMGIC mRNA, stimulation by serum results in a dramatic upregulation with the characteristics of a delayed-early response gene. Characterization of involved signal transduction pathways showed that both FGF-1 and PDGF-BB are strong inducers of HMGIC expression mediated via both the PI-3 kinase and MAP kinase pathways. In order to characterize the regulatory elements, sequences upstream of the translation initiation site of HMGIC were assayed for promoter activity. The HMGIC 5′ flanking sequences had constitutive promoter activity in all cell lines tested, suggesting that HMGIC is regulated by negative regulatory elements that were not present in the 5′-flanking regions analysed here.

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Acknowledgements

This work was supported by the ‘Fonds voor Wetenschappelijk Onderzoek, Vlaanderen’ (FWO), the ‘Geconcerteerde Onderzoekacties 1997 – 2001’, the ASLK ‘Programma voor Kankeronderzoek’. The authors are grateful to Isabelle Orlans and Veronique Wouters for excellent experimental assistance. The authors would like to thank Drs R Baserga and B Burgering for providing the IGF-I receptor and p21Ras expression constructs, respectively.

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  1. Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000, Belgium

    Torik AY Ayoubi, Erik Jansen, Sandra MP Meulemans & Wim JM Van de Ven

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  1. Torik AY Ayoubi
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Ayoubi, T., Jansen, E., Meulemans, S. et al. Regulation of HMGIC expression: an architectural transcription factor involved in growth control and development. Oncogene 18, 5076–5087 (1999). https://doi.org/10.1038/sj.onc.1202881

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