Activation of the p21Waf1/Cip1 promoter by the ets transcription factor E1AF

Funaoka, K.; Shindoh, Masanobu; Yoshida, Kazuya; Hanzawa, Motoaki; Hida, Kyoko; Nishikata, Shoji; Amemiya, Anne; Fujinaga, Koh; Totsuka, Yasunori

doi:10.1016/s0901-5027(97)81089-2

Cited by 10 publications

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“…ETV4 (E1AF or PEA3) is a member of the Ets-related transcription factor family and has been associated with both rapid cell growth (38) and invasion (39) in ovarian cancer. Platinum treatment has been reported to up-regulate ETV4 (40) and this change seems to have been maintained in the PE01 CDDP line with a 12-fold increase in expression compared with PE01. We observed increased ERK activity in the PE01 CDDP cells relative to PE01 cells and ERK is reported to regulate ETV4 (41).…”

Section: Discussionmentioning

confidence: 94%

Altered ErbB Receptor Signaling and Gene Expression in Cisplatin-Resistant Ovarian Cancer

et al. 2005

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The majority of ovarian cancer patients are treated with platinum-based chemotherapy, but the emergence of resistance to such chemotherapy severely limits its overall effectiveness. We have shown that development of resistance to this treatment can modify cell signaling responses in a model system wherein cisplatin treatment has altered cell responsiveness to ligands of the erbB receptor family. A cisplatinresistant ovarian carcinoma cell line PE01 CDDP was derived from the parent PE01 line by exposure to increasing concentrations of cisplatin, eventually obtaining a 20-fold level of resistance. Whereas PE01 cells were growth stimulated by the erbB receptor-activating ligands, such as transforming growth factor-A (TGFA), NRG1A, and NRG1B, the PE01 CDDP line was growth inhibited by TGFA and NRG1B but unaffected by NRG1A. TGFA increased apoptosis in PE01 CDDP cells but decreased apoptosis in PE01 cells. Differences in extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling were also found, which may be implicated in the altered cell response to ligands. Microarray analysis revealed 51 genes whose mRNA increased by at least 2-fold in PE01 CDDP cells relative to PE01 (including FRA1, ETV4, MCM2, AXL, MT3, TRAP1, and FANCG), whereas 36 genes (including IGFBP3, TRAM1, and KRT4 and KRT19) decreased by a similar amount. Differential display reverse transcriptase-PCR identified altered mRNA expression for TCP1, SLP1, proliferating cell nuclear antigen, and ZXDA. Small interfering RNA inhibition of FRA1, TCP1, and MCM2 expression was associated with reduced growth and FRA1 inhibition with enhanced cisplatin sensitivity. Altered expression of these genes by cytotoxic exposure may provide survival advantages to cells including deregulation of signaling pathways, which may be critical in the development of drug resistance. (Cancer Res 2005; 65(15): 6789-800)

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Section: Discussionmentioning

confidence: 94%

Altered ErbB Receptor Signaling and Gene Expression in Cisplatin-Resistant Ovarian Cancer

et al. 2005

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“…In human prostate carcinoma cell lines lacking wild-type p53, Lovastatim, an inhibitor of HMG-CoA reductase, transactivated p21 gene expression through an SP-1-binding site in the promoter and induced growth arrest in the G 1 phase (Lee et al, 1998). Furthermore, a recent report indicated that the ets-binding sites were located in the promoter region of p21 (Funaoka et al, 1997). We investigated the effect of the antisense oligonucleotides on transactivation of p21 by luciferase assay using the p21 promoter luciferase reporter construct.…”

Section: Discussionmentioning

confidence: 99%

Downregulation and forced expression of EWS-Fli1 fusion gene results in changes in the expression of G1regulatory genes

et al. 2001

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Chromosomal translocation t(11;22)(q24:q12) is detected in approximately 90% of tumours of the Ewing family (ET). This translocation results in EWS-Fli1 gene fusion which produces a EWS-Fli1 fusion protein acting as an aberrant transcriptional activator. We previously reported that the inhibition of EWS-Fli1 expression caused the G 0 /G 1 arrest of ET cells. We, therefore, hypothesized that EWS-Fli1 may affect the expression of G 1 regulatory genes. Downregulation of EWS-Fli1 fusion proteins was observed 48 hours after the treatment with EWS-Fli1 antisense oligonucleotides. The expressions of G 1 cyclins, cyclin D1 and cyclin E, were markedly decreased in parallel with the reduction of EWS-Fli1 fusion protein. On the other hand, the expression of p21 and p27, which are important cyclin-dependent kinase inhibitors (CKIs) for G 1 –S transition, was dramatically increased after the treatment with EWS-Fli1 antisense oligonucleotides. RT-PCR analysis showed that alteration of the expressions of the cyclins and CKIs occurred at the mRNA level. Furthermore, transfection of EWS-Fli1 cDNA to NIH3T3 caused transformation of the cells and induction of the expression of cyclin D1 and E. Clinical samples of ET also showed a high level of expression of cyclin D1 mRNA, whereas mRNAs for p21 and p27 were not detected in the samples. These findings strongly suggest that the G 1 –S regulatory genes may be involved in downstream of EWS-Fli1 transcription factor, and that the unbalanced expression of G 1 –S regulatory factors caused by EWS-Fli1 may lead to the tumorigenesis of ET. © 2001 Cancer Research Campaign http://www. bjcancer.com

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“…Although p21 expression was initially identified as being p53-dependent, a variety of transcription factors, including SP1/SP3, Smads, AP2, p150(Sal2), the vertebrate homologue of the Drosophila melanogaster homeotic transcription factor Spalt, sterol regulatory element-binding protein-1a, STATs, ets-related transcription factor E1AF, AP2, CAAT/enhancer binding protein a/h, Ets-1, and hepatocyte nuclear factor-4a, bind to specific cis-acting elements in the p21 promoter to activate transcription of the gene via a p53-independent mechanism (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). In addition, the region between À58 and À51 bp from the p21 transcription initiation site contains consensus early growth response-1 (Egr-1) binding sequences (EBS), which play a major role in regulating p21 transcription in response to resveratrol treatment in K562 cells (13) and to tamoxifen in MDA-MB-361 breast cancer cells (14).…”

Section: Introductionmentioning

confidence: 99%

p21Waf1/Cip1 Expression by Curcumin in U-87MG Human Glioma Cells: Role of Early Growth Response-1 Expression

et al. 2008

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Curcumin, a natural compound, is a well-known chemopreventive agent with potent anticarcinogenic activity in a wide variety of tumor cells. Curcumin inhibits cancer cell proliferation in part by suppressing cyclin D1 and inducing expression of the cyclin-dependent kinase inhibitor p21Waf1/Cip1 . Both p53-dependent and p53-independent mechanisms regulate p21Waf1/Cip1 expression, but the mechanism by which curcumin regulates p21Waf1/Cip1 expression remains unknown. Here, we report that transcription of the p21Waf1/Cip1 gene is activated by early growth response-1 (Egr-1) independently of p53 in response to curcumin treatment in U-87MG human glioblastoma cells. Egr-1 is a transcription factor that helps regulate differentiation, growth, and apoptosis in many cell types. Egr-1 expression is induced by curcumin through extracellular signal-regulated kinase (ERK) and c-Jun NH 2 -terminal kinase (JNK), but not the p38, mitogen-activated protein kinase (MAPK) pathways, which mediate the transactivation of Elk-1. Transient expression of Egr-1 enhanced curcumin-induced p21 Waf1/Cip1 promoter activity, whereas suppression of Egr-1 expression by small interfering RNA abrogated the ability of curcumin to induce p21 Waf1/Cip1 promoter activity. In addition, stable knockdown of Egr-1 expression in U-87MG cells suppressed curcumin-induced p21 expression. Our results indicate that ERK and JNK MAPK/Elk-1/Egr-1 signal cascade is required for p53-independent transcriptional activation of p21 Waf1/Cip1 in response to curcumin in U-87MG human glioblastoma cells. [Cancer Res 2008;68(5):1369-77]

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Activation of the p21Waf1/Cip1 promoter by the ets transcription factor E1AF

Cited by 10 publications

References 0 publications

Altered ErbB Receptor Signaling and Gene Expression in Cisplatin-Resistant Ovarian Cancer

Altered ErbB Receptor Signaling and Gene Expression in Cisplatin-Resistant Ovarian Cancer

Downregulation and forced expression of EWS-Fli1 fusion gene results in changes in the expression of G1regulatory genes

p21Waf1/Cip1 Expression by Curcumin in U-87MG Human Glioma Cells: Role of Early Growth Response-1 Expression

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