The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene.
BTG2/TIS21/PC3 protein is involved in the regulation of G1/S transition of the cell cycle by inhibiting pRb function, suggesting that BTG2/TIS21/PC3 regulation is critical for normal cell growth and proliferation. To understand the regulatory mechanisms for the expression of BTG2/TIS21/PC3 we cloned the human gene. Potential binding sites for several transcription factors were identified in the 5'-flanking region of the gene. Transient expression assays with BTG2/TIS21/PC3 promoter deletions and electrophoretic mobility shift analysis identified a major wild-type p53 response element located -74 to -122 relative to the start codon. This genomic fragment was sufficient to constitute a promoter element in the presence of p53. The BTG2/TIS21/PC3 gene is an antiproliferative gene which maps within a chromosomal segment (1q32) frequently altered in breast adenocarcinomas. However, no mutations of BTG2/TIS21/PC3 were detected in breast cancer cells, suggesting that the inactivation of this gene is not a frequent genetic event during breast carcinogenesis.
Duriez
Cyril
C
Unité INSERM U453, Unité d'Oncologie Moléculaire, Centre Léon Bérard, 28 rue Laënnec, F-69373 Lyon Cedex 08, France.
Falette
Nicole
N
Audoynaud
Carole
C
Moyret-Lalle
Caroline
C
Bensaad
Karim
K
Courtois
Stéphanie
S
Wang
Qing
Q
Soussi
Thierry
T
Puisieux
Alain
A
D001483:Base Sequence; D005786:Gene Expression Regulation; D005796:Genes / Q000235:genetics; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors / Q000235:genetics; D005838:Genotype; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D025521:Tumor Suppressor Proteins
D017874:Immediate-Early Proteins; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070114:BTG2 protein, human; D008156:Luciferases