Cytoplasmic HuR Expression Is a Prognostic Factor in Invasive Ductal Breast Carcinoma

Abstract

HuR is a ubiquitously expressed mRNA-binding protein.Intracellular localization of HuR is predominantly nuclear, but it shuttles between the nucleus and the cytoplasm. In the cytoplasm it can stabilize certain transcripts. Because nucleocytoplasmic translocation of HuR is necessary for its activity, it was hypothesized that cytoplasmic HuR expression in cancer cells could be a prognostic marker. To test the significance of HuR in carcinogenesis of the breast, we have investigated HuR expression in a mouse mammary gland tumor model and from 133 invasive ductal breast carcinoma specimens. HuR expression was elevated in the cyclooxygenase-2 transgene-induced mouse mammary tumors, and its expression was predominantly cytoplasmic in the tumor cells. In the human carcinoma samples, high cytoplasmic immunoreactivity for HuR was found in 29% (38 of 133) of the cases. Cytoplasmic HuR expression associated with high grade (P = 0.0050) and tumor size over 2 cm (P = 0.0082). Five-year distant disease-free survival rate was 42% [95% confidence interval (95% CI), 26-58] in cytoplasm-high category and 84% (95% CI, 76-91) in cytoplasm-negative or -low category (P < < 0.0001), and high cytoplasmic expression of HuR was an independent prognostic factor in a Cox multivariate model (relative risk 2.07; 95% CI, 1.05-4.07). Moreover, high cytoplasmic HuR immunopositivity was significantly associated with poor outcome in the subgroup of node-negative breast cancer in a univariate analysis (P < < 0.0007). Our results show that high cytoplasmic HuR expression is associated with a poor histologic differentiation, large tumor size, and poor survival in ductal breast carcinoma. Thus, HuR is the first mRNA stability protein of which expression associates with poor outcome in breast cancer. (Cancer Res 2005; 65(6): 2157-61)

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

“…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.…”

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

“…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.…”

“…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.…”

Taxa de sobrevida na mulher com câncer de mama: estudo de revisão

“…The publications originated from 20 countries: Korea (six studies), [8][9][10][11][12][13] Japan (five studies), [14][15][16][17][18] Brazil (four studies), 3,[19][20][21] Canada (three studies), [22][23][24] United States (three studies), [25][26][27] Italy (three studies), [28][29][30] Switzerland (three studies), [31][32][33] France (two studies), 34,35 China (one study), 36 Singapore and Sweden (one study, study performed in both countries), 37 Scotland (one study), 38 Spain (one study), 39 Finland (one study), 40 India (one study), 41 England (two studies), 42,45 Mexico (one study), 43 Poland (one study), 44 and the Netherlands (one study). 46 From the aim established for this study, the variables to be investigated were defined: the study design, study site/country, number of subjects, age of the subjects, five year survival rate, disease-free five year survival rate, factors that contribute to the increase in survival rates.…”