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Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells

Oncogene volume 19, pages 3411–3421 (2000)Cite this article

Abstract

Cancer is a progressive disease in which a tumor cell temporally develops qualitatively new transformation related phenotypes or a further elaboration of existing transformation associated properties. Subtraction hybridization identified a novel gene associated with transformation progression in mutant adenovirus type 5, H5ts125, transformed rat embryo cells, progression elevated gene-3 (PEG-3). To define the mechanism by which expression of PEG-3 is enhanced as a function of cancer progression a 5′-flanking promoter region of ∼2.0-kb, PEG-Prom, was isolated, cloned and characterized. The full-length and various mutated regions of the PEG-Prom were linked to a luciferase reporter construct and evaluated for promoter activity during cancer progression. These assays demonstrate a requirement for AP1 and PEA3 sites adjacent to the TATA box region of PEG-3 in mediating basal promoter activity and the enhanced expression of PEG-3 in progressed H5-ts125-transformed rat embryo cells. An involvement of AP1 and PEA3 in PEG-3 regulation was also confirmed by electrophoretic mobility shift assays (EMSA) and transfection studies with cJun and PEA3 expression vectors. Our findings document the importance of both AP1 and PEA3 transcription factors in mediating basal and elevated expression of PEG-3 in H5ts125-transformed rat embryo cells displaying an aggressive and progressed cancer phenotype.

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Acknowledgements

We thank Drs Rahul Gopalkrishnan and Dong-chul Kang for critical comments on this manuscript. We are grateful to Drs Michael Birrer and Paul Dent for providing the cJun and TAM67 expression vectors and Dr John Hassell for providing the PEA3 expression vector. This research was supported in part by National Institutes of Health Grants CA35675 and CA74468, the Chernow Endowment and the Samuel Waxman Cancer Research Foundation. PB Fisher is the Michael and Stella Chernow Urological Cancer Research Scientist.

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  1. Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University, College of Physicians and Surgeons, BB-15-1501, 630 West 168th Street, New York, 10032, NY, USA

    Zao-zhong Su, Yijie Shi & Paul B Fisher

  2. Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University, College of Physicians and Surgeons, BB-15-1501, 630 West 168th Street, New York, 10032, NY, USA

    Zao-zhong Su, Yijie Shi & Paul B Fisher

  3. Department of Neurosurgery, Herbert Irving Comprehensive Cancer Center, Columbia University, College of Physicians and Surgeons, BB-15-1501, 630 West 168th Street, New York, 10032, NY, USA

    Zao-zhong Su, Yijie Shi & Paul B Fisher

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Su, Zz., Shi, Y. & Fisher, P. Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells. Oncogene 19, 3411–3421 (2000). https://doi.org/10.1038/sj.onc.1203666

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