Cell Growth & Differentiation, Vol 5, Issue 8 801-809, Copyright © 1994 by American Association of Cancer Research

ARTICLES

Induction of epidermal growth factor receptor gene transcription by transforming growth factor beta 1: association with loss of protein binding to a negative regulatory element

X Hou, AC Johnson and MR Rosner
Ben May Institute, University of Chicago, IL 60637.

Transforming growth factor beta (TGF-beta) is a potent modulator of cell growth in many systems. In normal rat kidney fibroblasts, TGF-beta 1 increases epidermal growth factor (EGF) receptor gene transcription and synergizes with EGF to stimulate growth in soft agar, a characteristic of the transformed phenotype. In order to identify the target of TGF-beta 1 action, we have used a series of 5' deletion mutants of the EGF receptor promoter linked to a chloramphenicol acetyltransferase reporter gene (ERCAT). The TGF-beta response element(s) was localized to a cis-regulatory region which resides between positions -919 and -860 relative to the ATG translation initiation codon of the EGF receptor promoter. This 60-base pair region contains a repressor of the EGF receptor promoter and a TGF-beta inhibitory element that mediates TGF-beta 1 suppression of transin/stromelysin gene transcription through binding of a Fos-containing protein complex. Cotransfection of c-fos, c-jun, or both expression vectors with the intact or 5'-deleted ERCAT constructs identified several Fos-responsive inhibitory regions within the EGF receptor promoter, but these did not localize to the -919 to -860 promoter region. Mobility shift assays showed binding of the 60-base pair DNA fragment to proteins in extracts from untreated normal rat kidney cells; the binding was specifically competed by oligonucleotides containing a CAGATG sequence but not by oligonucleotides containing the EGF receptor repressor or the TGF-beta inhibitory element. TGF-beta 1 treatment but not anti-Fos antibody caused a decrease in specific 60-base pair DNA-protein complex formation.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				A. Kamat, P. M. Ghosh, R. L. Glover, B. Zhu, C.-K. Yeh, G. G. Choudhury, and M. S. Katz Reduced Expression of Epidermal Growth Factor Receptors in Rat Liver During Aging J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2008; 63(7): 683 - 692. [Abstract] [Full Text] [PDF]

				W. Liu, F. Innocenti, M. H. Wu, A. A. Desai, M. E. Dolan, E. H. Cook Jr., and M. J. Ratain A Functional Common Polymorphism in a Sp1 Recognition Site of the Epidermal Growth Factor Receptor Gene Promoter Cancer Res., January 1, 2005; 65(1): 46 - 53. [Abstract] [Full Text] [PDF]

				S. J. Kim, H. Uehara, S. Yazici, R. R. Langley, J. He, R. Tsan, D. Fan, J. J. Killion, and I. J. Fidler Simultaneous Blockade of Platelet-Derived Growth Factor-Receptor and Epidermal Growth Factor-Receptor Signaling and Systemic Administration of Paclitaxel as Therapy for Human Prostate Cancer Metastasis in Bone of Nude Mice Cancer Res., June 15, 2004; 64(12): 4201 - 4208. [Abstract] [Full Text] [PDF]

				H. Nishi, M. Senoo, K. H. Nishi, B. Murphy, T. Rikiyama, Y. Matsumura, S. Habu, and A. C. Johnson p53 Homologue p63 Represses Epidermal Growth Factor Receptor Expression J. Biol. Chem., November 2, 2001; 276(45): 41717 - 41724. [Abstract] [Full Text] [PDF]

				X.-W. Liu, Y. Katagiri, H. Jiang, L.-J. Gong, L.-Y. Guo, M. Shibutani, A. C. Johnson, and G. Guroff Cloning and Characterization of the Promoter Region of the Rat Epidermal Growth Factor Receptor Gene and Its Transcriptional Regulation by Nerve Growth Factor in PC12 Cells J. Biol. Chem., March 15, 2000; 275(10): 7280 - 7288. [Abstract] [Full Text] [PDF]

				A. L. Reed, H. Yamazaki, J. D. Kaufman, Y. Rubinstein, B. Murphy, and A. C. Johnson Molecular Cloning and Characterization of a Transcription Regulator with Homology to GC-binding Factor J. Biol. Chem., August 21, 1998; 273(34): 21594 - 21602. [Abstract] [Full Text] [PDF]

				H. Okada, T. M. Danoff, R. Kalluri, and E. G. Neilson Early role of Fsp1 in epithelial-mesenchymal transformation Am J Physiol Renal Physiol, October 1, 1997; 273(4): F563 - F574. [Abstract] [Full Text] [PDF]

				M. Lampl, N. Cameron, J. D. Veldhuis, and M. L. Johnson Response Science, April 21, 1995; 268(5209): 445 - 447. [PDF]