Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer

Sun, Xiaodong; Frierson, Henry F.; Chen, Ceshi; Li, Changling; Ran, Qimei; Otto, Kristen; Cantarel, Brandi M.; Vessella, Robert L.; Gao, Allen C.; Petros, John A.; Miura, Yutaka; Simons, Jonathan W.; Dong, Jin Tang

doi:10.1038/ng1528

Cited by 156 publications

(193 citation statements)

References 24 publications

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“…38 Moreover, ATBF1 was recently identified as a tumor suppressor gene. 19 These observations suggest that ATBF1 localization in the nucleus suppresses MUC5AC in gastric cancer and results in better prognosis. MUC5AC expression might be an indicator of the characteristics of different gastric cancers by associating with the function of ATBF1.…”

Section: Discussionmentioning

confidence: 85%

“…17,18 These observations are consistent with the recent identification of ATBF1 as a tumor suppressor. 19 Thus, not only the expression levels of ATBF1, but also its subcellular localization, appear to be linked to cell differentiation and induction of cell cycle arrest. 20 The present study of mucin expression in gastric cancer and the functions of ATBF1 [21][22][23] has revealed that the expression of ATBF1 in the nucleus suppresses MUC5AC expression in gastric cancer.…”

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confidence: 99%

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Subcellular localization of ATBF1 regulates MUC5AC transcription in gastric cancer

Mori

Kataoka

Miura

et al. 2007

Intl Journal of Cancer

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Human gastric epithelium has a unique mucin gene expression pattern, which becomes markedly altered in gastrointestinal disorder. This alteration in mucin expression, including the mucin MUC5AC, may be related to the development and prognosis of gastric cancers, and MUC5AC-positive gastric cancer has been reported to be poor prognosis. However, the molecular mechanism of MUC5AC transcriptional regulation has not been fully elucidated. AT motif-binding factor 1 (ATBF1) is a homeotic transcriptional regulatory factor recently identified as a tumor suppressor gene, and its subcellular localization suggests a link to cell proliferation and differentiation. We investigated the mechanism of MUC5AC transcriptional regulation by ATBF1. In 123 gastric cancer lesions, ATBF1 expressed in the nucleus significantly suppressed MUC5AC expression, as determined by immunohistochemistry. In addition, analysis of the MUC5AC promoter region revealed an AT motif-like element. This element was found to be essential for ATBF1 suppression of MUC5AC promoter activity as shown in a dual luciferase-reporter assay. Over-expressed ATBF1 also significantly suppressed endogenous MUC5AC protein expression in gastric cancer cells. Chromatin immunoprecipitation demonstrated that ATBF1 binds to the AT motif-like element in the MUC5AC promoter. These results indicate that ATBF1 in the nucleus negatively regulates the MUC5AC gene in gastric cancer by binding to an AT motif-like element in the MUC5AC promoter. ' 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 85%

mentioning

confidence: 99%

Subcellular localization of ATBF1 regulates MUC5AC transcription in gastric cancer

Mori

Kataoka

Miura

et al. 2007

Intl Journal of Cancer

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“…Using a microarray analysis and quantitative PCR validation (39) of TRAMP-AR pe-T877A/Y mice, we observed the expected alterations in tumor genes such as TERT and Cdk2 (40,41) and the tumor suppressor genes NKX3.1, ATBF1, and p21 (42,43) (Fig. S3).…”

Section: Discussionmentioning

confidence: 92%

Noncanonical Wnt signaling mediates androgen-dependent tumor growth in a mouse model of prostate cancer

Takahashi

Watanabe

Okada

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Prostate cancer development is associated with hyperactive androgen signaling. However, the molecular link between androgen receptor (AR) function and humoral factors remains elusive. A prostate cancer mouse model was generated by selectively mutating the AR threonine 877 into alanine in prostatic epithelial cells through Cre-ER T2 -mediated targeted somatic mutagenesis. Such AR point mutant mice (AR pe-T877A/Y ) developed hypertrophic prostates with responses to both an androgen antagonist and estrogen, although no prostatic tumor was seen. In prostate cancer model transgenic mice, the onset of prostatic tumorigenesis as well as tumor growth was significantly potentiated by introduction of the AR T877A mutation into the prostate. Genetic screening of mice identified Wnt-5a as an activator. Enhanced Wnt-5a expression was detected in the malignant prostate tumors of patients, whereas in benign prostatic hyperplasia such aberrant up-regulation was not obvious. These findings suggest that a noncanonical Wnt signal stimulates development of prostatic tumors with AR hyperfunction.antiandrogen | hormone-refractory state | TRAMP

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“…All tumor and matched normal cells were collected from H&E stained sections of formalin-fixed, paraffin-embedded tissues by manual microdissection, as described in our previous study (Dong et al, 2000). All prostatic epithelial cell lines and xenografts were described in our previous studies (Chen et al, 2003a, b;Sun et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer

et al. 2006

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The gene for E3 ubiquitin ligase WWP1 is located at 8q21, a region frequently amplified in human cancers, including prostate cancer. Recent studies have shown that WWP1 negatively regulates the TGFb tumor suppressor pathway by inactivating its molecular components, including Smad2, Smad4 and TbR1. These findings suggest an oncogenic role of WWP1 in carcinogenesis, but direct supporting evidence has been lacking. In this study, we examined WWP1 for gene dosage, mRNA expression, mutation and functions in a number of human prostate cancer samples. We found that the WWP1 gene had copy number gain in 15 of 34 (44%) xenografts and cell lines from prostate cancer and 15 of 49 (31%) clinical prostate cancer samples. Consistently, WWP1 was overexpressed in 60% of xenografts and cell lines from prostate cancer. Mutation of WWP1 occurred infrequently in prostate cancer. Functionally, WWP1 overexpression promoted colony formation in the 22Rv1 prostate cancer cell line. In PC-3 prostate cancer cells, WWP1 knockdown significantly suppressed cell proliferation and enhanced TGFb-mediated growth inhibition. These findings suggest that WWP1 is an oncogene that undergoes genomic amplification at 8q21 in human prostate cancer, and WWP1 overexpression is a common mechanism involved in the inactivation of TGFb function in human cancer.

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Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer

Cited by 156 publications

References 24 publications

Subcellular localization of ATBF1 regulates MUC5AC transcription in gastric cancer

Subcellular localization of ATBF1 regulates MUC5AC transcription in gastric cancer

Noncanonical Wnt signaling mediates androgen-dependent tumor growth in a mouse model of prostate cancer

Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer

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