The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene

Duriez, Cyril; Falette, Nicole; Audoynaud, Carole; Moyret‐Lalle, Caroline; Bensaad, Karim; Courtois, Stéphanie; Wang, Qing; Soussi, Thierry; Puisieux, Alain

doi:10.1016/s0378-1119(01)00825-3

Cited by 63 publications

(58 citation statements)

References 25 publications

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“…The induction of BTG2 in T47D cells, which contain a transactivation-deficient p53 allele mutated at codon 194 (Nigro et al, 1989;Wosikowski et al, 1995), suggests that BTG2 expression may be regulated through p53-independent mechanisms as well. The presence of an NF-kB site in the promoter region of BTG2 (Duriez et al, 2002) renders it responsive to signals such as MIS and TNF-a, which robustly induce NF-kB. The partial abrogation of BTG2 induction by MIS in T47D cells expressing dominant-negative IkB-a suggests that other transcription factors besides NF-kB may also be involved in MIS-mediated induction of BTG2.…”

Section: Discussionmentioning

confidence: 99%

“…The partial abrogation of BTG2 induction by MIS in T47D cells expressing dominant-negative IkB-a suggests that other transcription factors besides NF-kB may also be involved in MIS-mediated induction of BTG2. In fact characterization of the BTG2 promoter revealed the presence of putative DNA binding sites for many transcription factors including AP1, GATA1 and SP1 (Duriez et al, 2002). The kinetics of BTG2 induction is stimulus dependent.…”

Section: Discussionmentioning

confidence: 99%

“…Northern blot analysis of RNA isolated from T47D cells confirmed the induction of BTG2 by MIS (Figure 1a). Since we had previously demonstrated that MIS induces NF-kB DNA binding activity (Segev et al, , 2001(Segev et al, , 2002, and the BTG2 promoter is reported to have an NF-kB consensus DNA binding element (Duriez et al, 2002), we tested whether stimulation of BTG2 by MIS was mediated through activation of the NF-kB pathway. As shown in Figure 1a, upregulation of BTG2 mRNA by MIS was mitigated by the expression of dominant-negative IkB-a, suggesting that activation of the NF-kB pathway was required for this process ( Figure 1a).…”

Section: Activation Of Nf-kb Induces Btg2 Expression In Breast Cancermentioning

confidence: 99%

“…BTG2 is expressed predominantly in the epithelium of many tissues (Melamed et al, 2002) and can be regulated in response to DNA damage induced by UV, ionizing radiations and adriamycin, and by NGF, interleukin-6, 12-O-tetradecanoylphorbol-13-acetate, epidermal growth factor (EGF), serum and cAMP (Matsuda et al, 2001;Tirone, 2001). The expression of BTG2 is inducible by p53 (Rouault et al, 1996), and the presence of binding sites for nuclear factor kappa B (NF-kB), AP1 and GATA1 in the promoter of BTG2 (Duriez et al, 2002) suggests that it may also be responsive to stimuli that can activate transcription factors other than p53.…”

Section: Introductionmentioning

confidence: 99%

“…The BTG2 gene localizes to chromosomal locus 1q32 (Duriez et al, 2002), and loss of heterozygosity at 1q23-32 appears to be one of the lesions associated with development of breast cancer (Chen et al, 1989). However, little is known about the role of BTG2 in mammary gland development and tumorigenesis, and so far no mutations in the BTG2 gene have been reported in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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Expression of the NF-κB-responsive gene BTG2 is aberrantly regulated in breast cancer

et al. 2004

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BTG2, a p53-inducible antiproliferative gene, is stimulated in breast cancer cells by activation of nuclear factor kappa B (NF-jB). In rat mammary glands, BTG2 is expressed in epithelial cells and levels decreased during pregnancy and lactation but recovered during involution. Estrogen and progestin suppress BTG2 expression, suggesting that these steroids, which stimulate proliferation and lobuloalveolar development of mammary epithelial cells, may downregulate BTG2 in the mammary gland during pregnancy. Consistent with the report that BTG2 inhibits cyclin D1 expression, suppression of BTG2 mRNA in the mammary gland during gestation, and by estrogen and progestin, correlated with stimulation of cyclin D1. Ectopic expression of BTG2 inhibited breast cancer cell growth by arresting cells in the G1 phase, an effect reversed by cyclin D1. BTG2 expression was very low or undetectable in human breast cancer cell lines compared with nontumorigenic mammary epithelial cells, and nuclear expression of BTG2 was absent in 65% of human breast tumors compared with adjacent matched normal glands. Spontaneous mammary tumors arising in a mouse model with targeted expression of the early region of the SV40 large tumor Ag demonstrated loss of BTG2 protein very early during the tumorigenic process. Thus deregulation of BTG2 may be an important step in the development of mammary tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Activation Of Nf-kb Induces Btg2 Expression In Breast Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of the NF-κB-responsive gene BTG2 is aberrantly regulated in breast cancer

et al. 2004

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DNA damage sensible engineered promoter for cellular biosensing of cytotoxicity

Wada

Hamaguchi

Furukawa

et al. 2008

Biotech & Bioengineering

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We have established a cytotoxic sensor cell line by transfecting HepG2 cells with a luciferase protein plasmid derived from the heat shock protein 70B' (HSP70B') promoter, which is induced by cytotoxic reagents. HSP70B genes are up-regulated by a wide-range of cytotoxic stimulators, in particular, those that denature proteins. However, the HSP70B genes do not respond to DNA damage. We used a PCR array to detect marker genes of DNA damage-related cytotoxic stimulation and found the BTG2 gene to be one such gene. Analysis of the BTG2 gene functional promoter region by transfection of various deletion constructs into HepG2 cells indicated that the p53 and NFY biding sites on BTG2 are important for the response to DNA damage. We then constructed HepG2 sensor cells using the functional BTG2 promoter, and found that these sensor cells can specifically detect the cytotoxicity accompanied by DNA strand breaks with high sensitivity.

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BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells

et al. 2017

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Although widely deemed as a tumor suppressor gene, the role of B‐cell translocation gene 2 (BTG2) in bladder cancer is still inconclusive. We investigated the role and regulatory mechanism of BTG2 in bladder cancer. BTG2 expression in human bladder tissues was determined by RT‐qPCR and immunoblotting assays. Expressions of BTG2 and PTEN in bladder carcinoma cells were determined by immunoblotting, RT‐qPCR, or reporter assays. The 3H‐thymidine incorporation assay, flow cytometry, and the xenograft animal model were used to determine the cell growth. BTG2 expression was lower in human bladder cancer tissues than normal bladder tissues. Highly differentiated bladder cancer cells, RT4, expressed higher BTG2 than the less‐differentiated bladder cancer cells, HT1376 and T24. Overexpression of BTG2 in T24 cells inhibited cell growth in vitro and in vivo. Camptothecin and doxorubicin treatments in RT‐4 cells or transient overexpression of p53 into p53‐mutant HT1376 cells induced p53 and BTG2 expression. Further reporter assays with site‐mutation of p53 response element from GGGAAAGTCC to GGAGTCC within BTG2 promoter area showed that p53‐induced BTG2 gene expression was dependent on the p53 response element. Ectopic PTEN overexpression in T24 cells blocked the Akt signal pathway which attenuated cell growth via upregualtion of BTG2 gene expression, while reverse effect was found in PTEN‐knockdown RT‐4 cells. PTEN activity inhibitor (VO‐OHpic) treatment decreased BTG2 expression in RT‐4 and PTEN‐overexpressed T24 cells. Our results suggested that BTG2 functioned as a bladder cancer tumor suppressor gene, and was induced by p53 and PTEN. Modulation of BTG2 expression seems a promising way to treat human bladder cancer.

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The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene

Cited by 63 publications

References 25 publications

Expression of the NF-κB-responsive gene BTG2 is aberrantly regulated in breast cancer

Expression of the NF-κB-responsive gene BTG2 is aberrantly regulated in breast cancer

DNA damage sensible engineered promoter for cellular biosensing of cytotoxicity

BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells

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