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Cell Growth & Differentiation, Vol 8, Issue 7 751-762, Copyright © 1997 by American Association of Cancer Research
ARTICLES |
JN Parker, W Zhao, KJ Askins, TR Broker and LT Chow
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham 35294-0005, USA.
Human papillomaviruses (HPVs) reproduce only in differentiated squamous epithelia. Viral transcription is rather restricted in basal strata but increases dramatically in the spinous cells. Inopportune viral oncoprotein expression in the basal reserve cells can lead to dysplasias and carcinomas. Until now all studies to identify transcription factor binding sites within the upstream regulatory region (URR) that controls the expression of the oncogene have been conducted in proliferating cell cultures. We report the establishment of a reproducible and convenient system to examine cis elements important for differentiation-dependent transcriptional regulation. The bacterial lacZ gene under the control of the HPV URR-E6 promoter was transduced into primary human keratinocytes from neonatal foreskin by using high titer recombinant retroviruses. Acutely infected PHKs were then grown into stratified and differentiated epithelium on collagen rafts. lacZ expression was almost entirely restricted to the spinous cells, indicating that promoter activity was differentiation dependent, as seen in vivo. Using this system, we initiated a mutational analysis of previously identified promoter and enhancer elements within the HPV-18 URR. Three categories of mutation were observed: those that caused severe, moderate, or very small reduction in lacZ expressions. The results show both similarities and differences to previously published and present studies in proliferating primary human keratinocytes in monolayer cultures or in immortalized or transformed cell lines. This system is applicable to study both host and viral promoters that require squamous differentiation for their activity.
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E. Sen, S. Alam, and C. Meyers Genetic and Biochemical Analysis of cis Regulatory Elements within the Keratinocyte Enhancer Region of the Human Papillomavirus Type 31 Upstream Regulatory Region during Different Stages of the Viral Life Cycle J. Virol., January 15, 2004; 78(2): 612 - 629. [Abstract] [Full Text] [PDF]
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F. Noya, C. Balague, N. S. Banerjee, D. T. Curiel, T. R. Broker, and L. T. Chow Activation of Adenovirus Early Promoters and Lytic Phase in Differentiated Strata of Organotypic Cultures of Human Keratinocytes J. Virol., June 1, 2003; 77(11): 6533 - 6540. [Abstract] [Full Text] [PDF]
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J. L. Bromberg-White and C. Meyers The Upstream Regulatory Region of Human Papillomavirus Type 31 Is Insensitive to Glucocorticoid Induction J. Virol., August 28, 2002; 76(19): 9702 - 9715. [Abstract] [Full Text] [PDF]
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E. Sen, J. L. Bromberg-White, and C. Meyers Genetic Analysis of cis Regulatory Elements within the 5' Region of the Human Papillomavirus Type 31 Upstream Regulatory Region during Different Stages of the Viral Life Cycle J. Virol., April 16, 2002; 76(10): 4798 - 4809. [Abstract] [Full Text] [PDF]
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W.-M. Chien, F. Noya, H. M. Benedict-Hamilton, T. R. Broker, and L. T. Chow Alternative Fates of Keratinocytes Transduced by Human Papillomavirus Type 18 E7 during Squamous Differentiation J. Virol., February 22, 2002; 76(6): 2964 - 2972. [Abstract] [Full Text] [PDF]
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C. Balague, F. Noya, R. Alemany, L. T. Chow, and D. T. Curiel Human Papillomavirus E6E7-Mediated Adenovirus Cell Killing: Selectivity of Mutant Adenovirus Replication in Organotypic Cultures of Human Keratinocytes J. Virol., August 15, 2001; 75(16): 7602 - 7611. [Abstract] [Full Text] [PDF]
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F. Noya, W.-M. Chien, T. R. Broker, and L. T. Chow p21cip1 Degradation in Differentiated Keratinocytes Is Abrogated by Costabilization with Cyclin E Induced by Human Papillomavirus E7 J. Virol., July 1, 2001; 75(13): 6121 - 6134. [Abstract] [Full Text] [PDF]
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 S. A. Southern, F. Noya, C. Meyers, T. R. Broker, L. T. Chow, and C. S. Herrington Tetrasomy Is Induced by Human Papillomavirus Type 18 E7 Gene Expression in Keratinocyte Raft Cultures Cancer Res., June 1, 2001; 61(12): 4858 - 4863. [Abstract] [Full Text] [PDF]
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 W.-M. Chien, J. N. Parker, D.-C. Schmidt-Grimminger, T. R. Broker, and L. T. Chow Casein Kinase II Phosphorylation of the Human Papillomavirus-18 E7 Protein Is Critical for Promoting S-Phase Entry Cell Growth Differ., August 1, 2000; 11(8): 425 - 435. [Abstract] [Full Text]
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N. Zou, B. Y. Lin, F. Duan, K.-Y. Lee, G. Jin, R. Guan, G. Yao, E. J. Lefkowitz, T. R. Broker, and L. T. Chow The Hinge of the Human Papillomavirus Type 11 E2 Protein Contains Major Determinants for Nuclear Localization and Nuclear Matrix Association J. Virol., April 15, 2000; 74(8): 3761 - 3770. [Abstract] [Full Text]
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W. Stünkel, Z. Huang, S.-H. Tan, M. J. O'Connor, and H.-U. Bernard Nuclear Matrix Attachment Regions of Human Papillomavirus Type 16 Repress or Activate the E6 Promoter, Depending on the Physical State of the Viral DNA J. Virol., March 15, 2000; 74(6): 2489 - 2501. [Abstract] [Full Text]
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W. Zhao, F. Noya, W. Y. Chen, T. M. Townes, L. T. Chow, and T. R. Broker Trichostatin A Up-Regulates Human Papillomavirus Type 11 Upstream Regulatory Region-E6 Promoter Activity in Undifferentiated Primary Human Keratinocytes J. Virol., June 1, 1999; 73(6): 5026 - 5033. [Abstract] [Full Text]
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W. Stünkel and H.-U. Bernard The Chromatin Structure of the Long Control Region of Human Papillomavirus Type 16 Represses Viral Oncoprotein Expression J. Virol., March 1, 1999; 73(3): 1918 - 1930. [Abstract] [Full Text]
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Y. Jian, B. A. Van Tine, W.-M. Chien, G. M. Shaw, T. R. Broker, and L. T. Chow Concordant Induction of Cyclin E and p21cip1 in Differentiated Keratinocytes by the Human Papillomavirus E7 Protein Inhibits Cellular and Viral DNA Synthesis Cell Growth Differ., February 1, 1999; 10(2): 101 - 111. [Abstract] [Full Text]
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M. W. J. Sark, D. F. Fischer, E. de Meijer, P. van de Putte, and C. Backendorf AP-1 and Ets Transcription Factors Regulate the Expression of the Human SPRR1A Keratinocyte Terminal Differentiation Marker J. Biol. Chem., September 18, 1998; 273(38): 24683 - 24692. [Abstract] [Full Text] [PDF]
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K.-Y. Lee, T. R. Broker, and L. T. Chow Transcription Factor YY1 Represses Cell-Free Replication from Human Papillomavirus Origins J. Virol., June 1, 1998; 72(6): 4911 - 4917. [Abstract] [Full Text] [PDF]
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S.-H. Tan, D. Bartsch, E. Schwarz, and H.-U. Bernard Nuclear Matrix Attachment Regions of Human Papillomavirus Type 16 Point toward Conservation of These Genomic Elements in All Genital Papillomaviruses J. Virol., May 1, 1998; 72(5): 3610 - 3622. [Abstract] [Full Text] [PDF]
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R. D. M. Steenbergen, J. N. Parker, S. Isern, P. J. F. Snijders, J. M. M. Walboomers, C. J. L. M. Meijer, T. R. Broker, and L. T. Chow Viral E6-E7 Transcription in the Basal Layer of Organotypic Cultures without Apparent p21cip1 Protein Precedes Immortalization of Human Papillomavirus Type 16- and 18-Transfected Human Keratinocytes J. Virol., January 1, 1998; 72(1): 749 - 757. [Abstract] [Full Text] [PDF]
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
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| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cell Growth & Differentiation |
