Cytoplasmic HuR expression correlates with epithelial cancer cell but not with stromal cell cyclooxygenase-2 expression in mucinous ovarian carcinoma

Erkinheimo, Tiina-Liisa; Sivula, A; Lassus, Heini; Heinonen, Mira; Furneaux, Henry; Haglund, Caj; Bützow, Ralf; Ristimäki, Ari

doi:10.1016/j.ygyno.2005.04.047

Cited by 108 publications

(176 citation statements)

References 30 publications

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“…However, these isoforms were not observed in the colon cancer cells (data not shown). HuR was also significantly upregulated in the cancers, confirming previous reports (Dixon et al, 2001;Nabors et al, 2001;Erkinheimo et al, 2003). Details of colorectal adenocarcinoma and specific expression pattern for the three genes are presented in Supplementary Table 1.…”

Section: Rbm3 Is Induced In Colon Cancerssupporting

confidence: 87%

“…HuR, the best characterized factor regulates the stability of COX-2, IL-8 and VEGF mRNAs, resulting in their increased expression, thereby enhancing tumorigenesis (Myer et al, 1997;Fan and Steitz, 1998b;Peng et al, 1998;Blaxall et al, 2000;Dixon et al, 2001;Nabors et al, 2001;Denkert et al, 2004Denkert et al, , 2006Erkinheimo et al, 2005;Heinonen et al, 2005). However, more recently it is believed that cytoplasmic localization, rather than total amount, governs HuR activity (Blaxall et al, 2000;Erkinheimo et al, 2003Erkinheimo et al, , 2005Denkert et al, 2004Denkert et al, , 2006Heinonen et al, 2005). Here, we have identified RBM3 as a novel HuR interacting partner, whose expression is not only significantly upregulated in tumors, but is also localized in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

“…HuR is primarily nuclear, but can be induced to redistribute from the nucleus to the cytoplasm (Fan and Steitz, 1998a). Furthermore, cytoplasmic HuR expression in cancer cells has been suggested to be a prognostic marker for cancers (Erkinheimo et al, 2003(Erkinheimo et al, , 2005Lopez de Silanes et al, 2003;Heinonen et al, 2005;Denkert et al, 2006). Given the strong nuclear colocalization of HuR and RBM3, and that there is increased cytoplasmic localization of the protein in cancers, we next determined whether RBM3 also exhibits shuttling activity.…”

Section: Rbm3 Is Necessary For Overcoming Mitotic Catastrophementioning

confidence: 99%

“…RNA-binding protein HuR interacts with these ARE sequences to regulate the stability and translation of COX-2 mRNA (Dixon et al, 2000;Cok and Morrison, 2001). HuR is also upregulated in various cancers Erkinheimo et al, 2003;Denkert et al, 2004Denkert et al, , 2006.…”

Section: Introductionmentioning

confidence: 99%

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Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe

et al. 2008

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RNA-binding proteins play a key role in post-transcriptional regulation of mRNA stability and translation. We have identified that RBM3, a translation regulatory protein, is significantly upregulated in human tumors, including a stage-dependent increase in colorectal tumors. Forced RBM3 overexpression in NIH3T3 mouse fibroblasts and SW480 human colon epithelial cells increases cell proliferation and development of compact multicellular spheroids in soft agar suggesting the ability to induce anchorage-independent growth. In contrast, downregulating RBM3 in HCT116 colon cancer cells with specific siRNA decreases cell growth in culture, which was partially overcome when treated with prostaglandin E 2 , a product of cyclooxygenase (COX)-2 enzyme activity. Knockdown also resulted in the growth arrest of tumor xenografts. We have also identified that RBM3 knockdown increases caspase-mediated apoptosis coupled with nuclear cyclin B1, and phosphorylated Cdc25c, Chk1 and Chk2 kinases, implying that under conditions of RBM3 downregulation, cells undergo mitotic catastrophe. RBM3 enhances COX-2, IL-8 and VEGF mRNA stability and translation. Conversely, RBM3 knockdown results in loss in the translation of these transcripts. These data demonstrate that the RNA stabilizing and translation regulatory protein RBM3 is a novel proto-oncogene that induces transformation when overexpressed and is essential for cells to progress through mitosis.

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Section: Rbm3 Is Induced In Colon Cancerssupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Rbm3 Is Necessary For Overcoming Mitotic Catastrophementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe

et al. 2008

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“…In other types of cancer, we and others have shown in recent studies that HuR is increased in breast cancer, 22,23 ovarian cancer, 15,24 glioblastoma multiforme and medulloblastoma 25 as well as in lung carcinoma cell lines. 26 In our study, we found that COX-2 is increased in a subset of colorectal adenocarcinomas.…”

Section: Discussionmentioning

confidence: 75%

Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2

et al. 2006

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There is growing body of evidence that post-translational events contribute-in addition to genetic changes-to the progression of malignant tumors. These post-translational alterations may provide targets for new therapeutic approaches. The ELAV-like protein HuR stabilizes a group of cellular mRNAs which contain AU-rich elements in their 3 0 untranslated region. To investigate a possible contribution of post-translational changes to the progression of colon cancer and to overexpression of COX-2, we studied expression of HuR and COX-2 a cohort of colorectal adenocarcinomas and in colon cancer cell lines. All cell lines showed an expression of HuR mRNA and protein. In tumor tissue of colon carcinomas we observed two different staining patterns of HuR: A nuclear expression in 98% as well as an additional cytoplasmic expression in 53% of cases. COX-2 was expressed in 63% of carcinomas. Cytoplasmic expression of HuR was significantly associated with increased COX-2 expression as well as with high tumor stage. In univariate Kaplan-Meier analysis, grading, tumor stage and nodal status but not HuR or COX-2 expression were prognostic factors for overall survival. Our results suggest that the overexpression of HuR in colon cancer may be part of a regulatory pathway that controls the mRNA stability of cyclooxygenase-2 and provides an interesting example for a contribution of a dysregulation of mRNA stability to the progression of colorectal cancer. Based on our results, further studies are necessary to investigate whether HuR might be a potential target for a molecular tumor therapy.

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The new standard of HCV therapy: Retreatment in experienced patients†,‡

Gara

Ghany

2012

Clinical Liver Disease

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Cytoplasmic HuR expression correlates with epithelial cancer cell but not with stromal cell cyclooxygenase-2 expression in mucinous ovarian carcinoma

Cited by 108 publications

References 30 publications

Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe

Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe

Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2

The new standard of HCV therapy: Retreatment in experienced patients†,‡

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