CELL-TYPE-SPECIFIC ACTIVITY OF THE HUMAN PAPILLOMAVIRUS TYPE-18 UPSTREAM REGULATORY REGION IN TRANSGENIC MICE AND ITS MODULATION BY TETRADECANOYL PHORBOL ACETATE AND GLUCOCORTICOIDS

被引:25
作者
CID, A [1 ]
AUEWARAKUL, P [1 ]
GARCIACARRANCA, A [1 ]
OVSEIOVICH, R [1 ]
GAISSERT, H [1 ]
GISSMANN, L [1 ]
机构
[1] NATL AUTONOMOUS UNIV MEXICO, INST INVEST BIOMED, MEXICO CITY 04510, DF, MEXICO
关键词
D O I
10.1128/JVI.67.11.6742-6752.1993
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The upstream regulatory region (URR) of human papillomavirus type 18 (HPV-18) harbors transcriptional promoter and enhancer elements which are thought to determine the cell-type specificity of the virus. In order to study the regulation of HPV-18 expression in vivo, we constructed transgenic mice carrying the bacterial lacZ gene under the control of the HPV-18 URR. Analysis of beta-galactosidase activity by histochemical staining of tissue sections of four independent transgenic mice showed that the viral promoter was specifically active in epithelial cells within a variety of organs (e.g., tongue, ovary, uterus, testis, and small intestine). Very strong staining was observed in newborn transgenic mice in contrast to a weak activity found during fetal life. Determination of beta-galactosidase activity in crude extracts from tissues of three lines of transgenic mice proved to be a useful tool for a quantitative analysis of transgene expression. In mice from two different transgenic lines treated with dexamethasone such measurements revealed a biphasic effect of the hormone on the activity of the enzyme in the stratified epithelium of the tongue (transient increase followed by a decrease). Northern (RNA) blot analysis showed similar changes in beta-galactosidase mRNA in that tissue. Treatment with tetradecanoyl phorbol acetate (TPA) led to a twofold increase in both enzymatic activity and mRNA levels. Finally, combined treatments with dexamethasone and TPA showed that both factors interfered with each other in their respective effects on transgene expression, suggesting that a cross-talk mechanism between transcription factors could be involved in the regulation of the HPV-18 URR.
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页码:6742 / 6752
页数:11
相关论文
共 61 条
  • [1] ANDERSON MLM, 1985, NUCLEIC ACID HYBRIDI, P73
  • [2] THE ROLE OF JUN, FOS AND THE AP-1 COMPLEX IN CELL-PROLIFERATION AND TRANSFORMATION
    ANGEL, P
    KARIN, M
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (2-3) : 129 - 157
  • [3] [Anonymous], 1986, MANIPULATING MOUSE E
  • [4] ARMBRUSTERMORAE.E, IN PRESS AM J OBSTET
  • [5] RETINOIC ACID-MEDIATED REPRESSION OF HUMAN PAPILLOMAVIRUS-18 TRANSCRIPTION AND DIFFERENT LIGAND REGULATION OF THE RETINOIC ACID RECEPTOR BETA-GENE IN NONTUMORIGENIC AND TUMORIGENIC HELA HYBRID-CELLS
    BARTSCH, D
    BOYE, B
    BAUST, C
    HAUSEN, HZ
    SCHWARZ, E
    [J]. EMBO JOURNAL, 1992, 11 (06) : 2283 - 2291
  • [6] IDENTIFICATION OF A NEGATIVE REGULATORY DOMAIN IN THE HUMAN PAPILLOMAVIRUS TYPE-18 PROMOTER - INTERACTION WITH THE TRANSCRIPTIONAL REPRESSOR-YY1
    BAUKNECHT, T
    ANGEL, P
    ROYER, HD
    HAUSEN, HZ
    [J]. EMBO JOURNAL, 1992, 11 (12) : 4607 - 4617
  • [7] THE E6-E7 REGION OF HUMAN PAPILLOMAVIRUS TYPE-18 IS SUFFICIENT FOR TRANSFORMATION OF NIH-3T3 AND RAT-1 CELLS
    BEDELL, MA
    JONES, KH
    LAIMINS, LA
    [J]. JOURNAL OF VIROLOGY, 1987, 61 (11) : 3635 - 3640
  • [8] IDENTIFICATION OF HUMAN PAPILLOMAVIRUS TYPE-18 TRANSFORMING GENES IN IMMORTALIZED AND PRIMARY-CELLS
    BEDELL, MA
    JONES, KH
    GROSSMAN, SR
    LAIMINS, LA
    [J]. JOURNAL OF VIROLOGY, 1989, 63 (03) : 1247 - 1255
  • [9] THE HUMAN PAPILLOMAVIRUS TYPE-18 (HPV18) E2 GENE-PRODUCT IS A REPRESSOR OF THE HPV18 REGULATORY REGION IN HUMAN KERATINOCYTES
    BERNARD, BA
    BAILLY, C
    LENOIR, MC
    DARMON, M
    THIERRY, F
    YANIV, M
    [J]. JOURNAL OF VIROLOGY, 1989, 63 (10) : 4317 - 4324
  • [10] A NEW TYPE OF PAPILLOMAVIRUS DNA, ITS PRESENCE IN GENITAL CANCER BIOPSIES AND IN CELL-LINES DERIVED FROM CERVICAL-CANCER
    BOSHART, M
    GISSMANN, L
    IKENBERG, H
    KLEINHEINZ, A
    SCHEURLEN, W
    HAUSEN, HZ
    [J]. EMBO JOURNAL, 1984, 3 (05) : 1151 - 1157