Is nuclear expression of Y box-binding protein-1 a new prognostic factor in ovarian serous adenocarcinoma?

Kamura, Toshiharu; Yahata, Hideaki; Amada, Satoshi; Ogawa, Shinji; Sonoda, T.; Kobayashi, Hiroaki; Mitsumoto, Masamune; Kohno, Kimitoshi; Kuwano, Michihiko; Nakano, Hitoo

doi:10.1002/(sici)1097-0142(19990601)85:11<2450::aid-cncr21>3.0.co;2-u

Cited by 103 publications

(111 citation statements)

References 15 publications

(15 reference statements)

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“…Suppression of YB-1 leads to an enhancement of MDR-1 expression and decrease of CXCR-4 expression We previously reported that YB-1 was expressed in the nucleus in almost 30% of serous ovarian cancers, and that YB-1 nuclear-positive patients had a poor prognosis (Kamura et al, 1999). As nuclear translocation of YB-1 is highly susceptible to environmental stimuli, we first examined whether the stress-inducing exogenous addition of serum could stimulate nuclear translocation of YB-1 in seven serum-deprived human ovarian cancer cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…Jiang et al (2006) further demonstrated that CXCR4 expression could be an important prognostic marker for ovarian cancers: the rate of CXCR4 expression in refractory and recurrent group was significantly higher than that in nonrecurrent group. Our previous studies showed a significant association of nuclear localization of YB-1 with unfavorable prognosis of patients with ovarian cancers (Kamura et al, 1999;Huang et al, 2004). Clinicopathological analysis whether nuclear expression of YB-1 can be associated with CXCR4 expression or CXCL12 (SDF-1a) in patients with ovarian cancers is now in progress.…”

Section: Discussionmentioning

confidence: 95%

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Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells

et al. 2006

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Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 (ABCB1) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells

et al. 2006

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“…The dbpA gene was first identified in 1988 (Sakura et al, 1988) and cloned in 1995, encoding a protein highly expressed in skeletal muscle (Kudo et al, 1995), and that of dbpC/contrin was cloned in 1999 as coding for a testis-specific protein distinct from other Y-box-binding proteins . The ubiquitous expression of the dbpB/YB-1 gene in human normal and neoplastic tissues has been well studied and found to be closely associated with the expression of p-glycoprotein, the product of the multidrug resistance 1 (MDR1) gene, in breast cancers (Bargou et al, 1997), osteosarcomas (Oda et al, 1998), ovarian cancers (Kamura et al, 1999), and synovial sarcomas (Oda et al, 2003). It is also associated with the expression of DNA topoisomerase II and proliferating cell nuclear antigen in colon (Shibao et al, 1999) and lung (Gu et al, 2001) cancers.…”

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confidence: 99%

Expression of Y-box-binding protein dbpC/contrin, a potentially new cancer/testis antigen

et al. 2006

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Y-box-binding proteins are members of the human cold-shock domain protein superfamily, which includes dbpA, dbpB/YB-1, and dbpC/contrin. dbpC/contrin is a germ cell-specific Y-box-binding protein and is suggested to function as a nuclear transcription factor and RNA-binding protein in the cytoplasm. Whereas ubiquitous dbpB/YB-1 expression has been well studied in various types of human carcinomas as a prognostic or predictive marker, the dbpC/contrin expression in human tumour cells has not been reported. In this report, we provide the first evidence showing that dbpC was highly expressed in human testicular seminoma and ovarian dysgerminomas, and in carcinomas in other tissues and that its expression in normal tissues is nearly restricted to germ cells and placental trophoblasts. These results indicate that dbpC/contrin would be a potentially novel cancer/testis antigen.

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“…Nuclear YB-1 expression has been linked to poorer prognosis compared to tumors with cytoplasmic YB-1 expression in breast cancer, non-small cell lung cancer, ovarian cancer, synovial sarcoma and hepatocellular carcinoma. 15,17,18,[23][24][25] Huang et al 26 found a signifi- cant correlation between coexpression of YB-1 and Pgp and poorer survival in ovarian cancer. In this study, YB-1 immunostaining had no significant correlation with age, sex, histopathological subtype, AJCC staging, tumor grade, nodal status and distant metastasis.…”

Section: Discussionmentioning

confidence: 97%

“…Studies conducted in breast cancer, non-small cell lung cancer, ovarian cancer and osteosarcoma have shown the presence of concomitant nuclear YB-1 expression together with cytoplasmic localization of the protein. 12,[17][18][19] We have not found distinct nuclear YB-1 staining in CNE-2 cells and nasopharyngeal cancer tissues. Although it is possible that the anti-K13 antibody which was used in this study, recognizes only the cytoplasmic epitope of YB-1, we consider the possibility unlikely because translocation of YB-1 to the nuclei in human HeLa cells has been detected by immunofluorescence using the same anti-YB-1 antibody (Matsumoto K, unpublished results).…”

Section: Discussionmentioning

confidence: 99%

Y-Box-binding protein-1 is a promising predictive marker of radioresistance and chemoradioresistance in nasopharyngeal cancer

et al. 2009

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The Y-Box-binding protein-1, a member of the cold-shock domain DNA-and RNA-binding protein superfamily, is known to mediate chemoresistance. The aim of this study was to determine the expression of Y-Box- Y-Box-binding protein-1 immunostaining was observed to be predominantly cytoplasmic. A higher recurrence of nasopharyngeal cancer was found in patients whose tissues had increased Y-Box-binding protein-1 expression (Po0.001). The Cox proportionate hazard regression model also established that high Y-Box-binding protein-1 immunoreactivity was significantly correlated with increased risk (2.13 times) of recurrence as compared to low Y-Box-binding protein-1 immunoreactivity (P ¼ 0.01). Within groups of patients treated by radiotherapy or chemoradiotherapy, recurrent cases had significantly higher Y-Box-binding protein-1 expression than nonrecurrent cases (Po0.001 and P ¼ 0.0035, respectively). These data suggest that Y-Box-binding protein-1 expression has clinicopathological significance with potential as a predictive marker of recurrence in nasopharyngeal cancer patients who undergo radiotherapy or chemoradiotherapy.

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Is nuclear expression of Y box-binding protein-1 a new prognostic factor in ovarian serous adenocarcinoma?

Cited by 103 publications

References 15 publications

Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells

Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells

Expression of Y-box-binding protein dbpC/contrin, a potentially new cancer/testis antigen

Y-Box-binding protein-1 is a promising predictive marker of radioresistance and chemoradioresistance in nasopharyngeal cancer

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