Molecular Endocrinology, Vol 9, 1610-1620, Copyright © 1995 by Endocrine Society

ARTICLES

Characterization of an early growth response gene, which encodes a zinc finger transcription factor, potentially involved in cell cycle regulation

LJ Blok, ME Grossmann, JE Perry and DJ Tindall
Department of Urology Research, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.

Using differential display polymerase chain reaction, early growth response gene alpha (EGR alpha) was first isolated as a 291-base pair 3'-cDNA clone, which was highly expressed in the androgen-independent prostate carcinoma cell lines PC3 and DU145, as compared with the androgen-responsive prostate carcinoma cell line LNCaP. Full length cloning of the EGR alpha coding region revealed that EGR alpha was a new member of an important subfamily of nuclear zinc finger transcription factors (others members e.g. Sp1, EGR-2, and Wilms' tumor gene). Moreover, it was observed that EGR alpha, as with most Sp1 subfamily members, was conserved between mammalian species ranging from human to rabbit. Two hormones important for prostate development and differentiation were found to be potent regulators of EGR alpha mRNA expression. Androgens were observed to induce a down-regulation of EGR alpha mRNA expression (70% in 72 h), while epidermal growth factor induced a rapid transient up-regulation (6-fold in 100 min). The up- regulation was controlled at the transcriptional level and effectively blocked by staurosporine (which suggests the involvement of the protein kinase C pathway). Functional analysis demonstrated that EGR alpha could bind to, and stimulate transcription from, a basic transcription element (BTE) consensus sequence on DNA (BTE is a transcription- modulating sequence in the promoter region of some cytochrome P450 family members). Furthermore, in stage-synchronized prostate cells, EGR alpha mRNA was highly expressed in the early G1 phase of the cell cycle, similar to c-fos mRNA expression. These results indicated that the zinc finger transcription factor EGR alpha seems to play a role in cell cycle regulation.

This article has been cited by other articles:

				A. P. W. Funnell, C. A. Maloney, L. J. Thompson, J. Keys, M. Tallack, A. C. Perkins, and M. Crossley Erythroid Kruppel-Like Factor Directly Activates the Basic Kruppel-Like Factor Gene in Erythroid Cells Mol. Cell. Biol., April 1, 2007; 27(7): 2777 - 2790. [Abstract] [Full Text] [PDF]

				P Hanifi-Moghaddam, B Sijmons, M C Ott, W F J van IJcken, D Nowzari, E C M Kuhne, P van der Spek, H J Kloosterboer, C W Burger, and L J Blok The hormone replacement therapy drug tibolone acts very similar to medroxyprogesterone acetate in an estrogen-and progesterone-responsive endometrial cancer cell line J. Mol. Endocrinol., December 1, 2006; 37(3): 405 - 413. [Abstract] [Full Text] [PDF]

				S. C.J.P. Gielen, C. W. Burger, L. C.M. Kuhne, P. Hanifi-Moghaddam, and L. J. Blok Analysis off Estrogen Agonism and Antagonism of Tamoxifen, Raloxifene, and ICI182780 in Endometrial Cancer Cells: A Putative Role for the Epidermal Growth Factor Receptor Ligand Amphiregulin Reproductive Sciences, October 1, 2005; 12(7): e55 - e66. [Abstract] [PDF]

				E. Smid-Koopman, L. C. M. Kuhne, E. E. Hanekamp, S. C.J.P. Gielen, P. E. De Ruiter, J. A. Grootegoed, T. J.M. Helmerhorst, C. W. Burger, A. O. Brinkmann, F. J. Huikeshoven, et al. Progesterone-Induced Inhibition of Growth and Differential Regulation of Gene Expression in PRA- and/or PRB-Expressing Endometrial Cancer Cell Lines Reproductive Sciences, May 1, 2005; 12(4): 285 - 292. [Abstract] [PDF]

				K. Thomas, D.-Y. Sung, J. Yang, K. Johnson, W. Thompson, C. Millette, J. McCarrey, A. Breitberg, R. Gibbs, and W. Walker Identification, Characterization, and Functional Analysis of Sp1 Transcript Variants Expressed in Germ Cells During Mouse Spermatogenesis Biol Reprod, April 1, 2005; 72(4): 898 - 907. [Abstract] [Full Text] [PDF]

				J. K Oosterhoff, J A. Grootegoed, and L. J Blok Expression profiling of androgen-dependent and -independent LNCaP cells: EGF versus androgen signalling Endocr. Relat. Cancer, March 1, 2005; 12(1): 135 - 148. [Abstract] [Full Text] [PDF]

				S. C.J.P. Gielen, E. E. Hanekamp, L. J. Blok, F. J. Huikeshoven, and C. W. Burger Steroid-Modulated Proliferation of Human Endometrial Carcinoma Cell Lines: Any Role for Insulin-like Growth Factor Signaling? Reproductive Sciences, January 1, 2005; 12(1): 58 - 64. [Abstract] [PDF]

				J. D. Noti, A. K. Johnson, and J. D. Dillon The Zinc Finger Transcription Factor Transforming Growth Factor {beta}-Inducible Early Gene-1 Confers Myeloid-specific Activation of the Leukocyte Integrin CD11d Promoter J. Biol. Chem., June 25, 2004; 279(26): 26948 - 26958. [Abstract] [Full Text] [PDF]

				B. F. Hinnebusch, A. Siddique, J. W. Henderson, M. S. Malo, W. Zhang, C. P. Athaide, M. A. Abedrapo, X. Chen, V. W. Yang, and R. A. Hodin Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor Am J Physiol Gastrointest Liver Physiol, January 1, 2004; 286(1): G23 - G30. [Abstract] [Full Text] [PDF]

				L. J. Blok, P. E. De Ruiter, E. C. M. Kuhne, E. E. Hanekamp, J. A. Grootegoed, E. Smid-Koopman, S. C. J. P. Gielen, M. E. De Gooyer, H. J. Kloosterboer, and C. W. Burger Progestagenic Effects of Tibolone on Human Endometrial Cancer Cells J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2327 - 2334. [Abstract] [Full Text] [PDF]

				E. Smid-Koopman, L. J. Blok, L. C. M. Kuhne,, C. W. Burger, T. J. M. Helmerhorst, A. O. Brinkman, and F. J. Huikeshoven Distinct Functional Differences of Human Progesterone Receptors A and B on Gene Expression and Growth Regulation in Two Endometrial Carcinoma Cell Lines Reproductive Sciences, January 1, 2003; 10(1): 49 - 57. [Abstract] [PDF]

				Y. Zhao, B. P. C. Chen, H. Miao, S. Yuan, Y.-S. Li, Y. Hu, D. M. Rocke, and S. Chien Improved significance test for DNA microarray data: temporal effects of shear stress on endothelial genes Physiol Genomics, December 26, 2002; 12(1): 1 - 11. [Abstract] [Full Text] [PDF]

				H. Qi, C. Fillion, Y. Labrie, J. Grenier, A. Fournier, L. Berger, M. El-Alfy, and C. Labrie AIbZIP, a Novel bZIP Gene Located on Chromosome 1q21.3 That Is Highly Expressed in Prostate Tumors and of Which the Expression Is Up-Regulated by Androgens in LNCaP Human Prostate Cancer Cells Cancer Res., February 1, 2002; 62(3): 721 - 733. [Abstract] [Full Text] [PDF]

				T. Cook and R. Urrutia TIEG proteins join the Smads as TGF-beta -regulated transcription factors that control pancreatic cell growth Am J Physiol Gastrointest Liver Physiol, April 1, 2000; 278(4): G513 - G521. [Abstract] [Full Text] [PDF]

				T. Cook, B. Gebelein, M. Belal, K. Mesa, and R. Urrutia Three Conserved Transcriptional Repressor Domains Are a Defining Feature of the TIEG Subfamily of Sp1-like Zinc Finger Proteins J. Biol. Chem., October 8, 1999; 274(41): 29500 - 29504. [Abstract] [Full Text] [PDF]

				T. Cook, B. Gebelein, K. Mesa, A. Mladek, and R. Urrutia Molecular Cloning and Characterization of TIEG2 Reveals a New Subfamily of Transforming Growth Factor-beta -inducible Sp1-like Zinc Finger-encoding Genes Involved in the Regulation of Cell Growth J. Biol. Chem., October 2, 1998; 273(40): 25929 - 25936. [Abstract] [Full Text] [PDF]

				T. Matsuba, N. Keicho, Y. Higashimoto, S. Granleese, J. C. Hogg, S. Hayashi, and G. P. Bondy Identification of Glucocorticoid- and Adenovirus E1A-regulated Genes in Lung Epithelial Cells by Differential Display Am. J. Respir. Cell Mol. Biol., February 1, 1998; 18(2): 243 - 254. [Abstract] [Full Text]

				M. M. Ahmed, S. F. Sells, K. Venkatasubbarao, S. M. Fruitwala, S. Muthukkumar, C. Harp, M. Mohiuddin, and V. M. Rangnekar Ionizing Radiation-inducible Apoptosis in the Absence of p53 Linked to Transcription Factor EGR-1 J. Biol. Chem., December 26, 1997; 272(52): 33056 - 33061. [Abstract] [Full Text] [PDF]

				S. Yajima, C.-H. Lammers, S.-H. Lee, Y. Hara, K. Mizuno, and M. M. Mouradian Cloning and Characterization of Murine Glial Cell-Derived Neurotrophic Factor Inducible Transcription Factor (MGIF) J. Neurosci., November 15, 1997; 17(22): 8657 - 8666. [Abstract] [Full Text] [PDF]

				J. M. Shields and V. W. Yang Two Potent Nuclear Localization Signals in the Gut-enriched Kruppel-like Factor Define a Subfamily of Closely Related Kruppel Proteins J. Biol. Chem., July 18, 1997; 272(29): 18504 - 18507. [Abstract] [Full Text] [PDF]