Induction of differentiation-regulated transcription factor Oct-6 specifically accompanies major histocompatibility complex class I down-regulation by E1A of oncogenic adenovirus type 12.
The E1A genes from adenovirus (Ad) types 5 and 12 share the capacity to cooperate with a second oncogene to transform primary rodent cells in vitro. However, only Ad12-transformed cells are oncogenic in immunocompetent rodents, an event that requires conserved region 3 (CR3) of E1A to be intact. Ad12-induced tumorigenicity correlates with the E1A-CR3-dependent down-modulation of MHC class I transcription, contributing to escape from CTL-mediated immune surveillance. Expression of MHC class I antigens is also lacking in undifferentiated embryonal carcinoma cells. In these cells, MHC class I expression increases during differentiation in a process possibly involving octamer-binding proteins. We found that both nononcogenic and oncogenic Ad-transformed cells contained the ubiquitously expressed factor Oct-1. In contrast, only oncogenic Ad12-transformed cells that are derived from primary cell cultures expressed an additional octamer-binding factor, which we identified as Oct-6. The induction of Oct-6 expression was at the RNA level and was found to require an intact CR3 domain in Ad12 E1A. Like MHC class I expression, Oct-6 expression was not affected in already established cell lines expressing Ad12 E1A. The presence of Oct-6 in Ad12-transformed cells correlated with an increase in octamer-dependent transcription of a reporter gene, relative to Ad5-transformed cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Molecular Carcinogenesis, Sylvius Laboratory, University of Leiden, The Netherlands.
D S
DS
Peeper
G J
GJ
Schouten
M
M
Toebes
D
D
Meijer
R
R
Zwart
I
I
van de Woude
H
H
van Schaik
A J
AJ
van der Eb
A
A
Zantema
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D050816:Octamer Transcription Factor-6; D051381:Rats; D012097:Repressor Proteins / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis*; D015533:Transcriptional Activation
D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; C494178:POU3F1 protein, human; C494179:Pou3f1 protein, rat; D012097:Repressor Proteins; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6