Transcription of dbpA, a Y box binding protein, is positively regulated by E2F1: implications in hepatocarcinogenesis

Arakawa, Yasuo; Kajino, Kazunori; Kano, Sayaka; Tobita, Hiroshi; Hayashi, J.; Yasen, Mahamute; Moriyama, Mitsuhiko; Arakawa, Yasuyuki; Hino, Okio

doi:10.1016/j.bbrc.2004.04.208

Cited by 37 publications

(34 citation statements)

References 31 publications

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“…In tumors such mutually exclusive alterations are found frequently for genes/proteins that are involved in a similar signaling pathway (32,33), suggesting that overexpression of symplekin or ZONAB could have similar consequences for tumorigenesis. Although E2F1-mediated transcriptional stimulation (34), as well as the presence of mutations and polymorphism in the ZONAB/ DbpA promoter (35), has been suggested as a cause for the increased transcriptional activity detected in hepatocarcinoma, the reasons underlying symplekin overexpression remain to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Symplekin promotes tumorigenicity by up-regulating claudin-2 expression

Büchert

Papin

Bonnans

et al. 2010

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

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Symplekin is a ubiquitously expressed protein involved in cytoplasmic RNA polyadenylation and transcriptional regulation and is localized at tight junctions (TJs) in epithelial cells. Nuclear symplekin cooperates with the Y-box transcription factor zonula occludens 1-associated nucleic acid-binding protein (ZONAB) to increase the transcription of cell cycle-related genes and also inhibits differentiation of intestinal cells. We detected high levels of nuclear symplekin in 8 of 12 human colorectal cancer (CRC) samples. shRNAmediated reduction of symplekin expression was sufficient to decrease significantly the anchorage-independent growth and proliferation of HT-29 CRC cells as well as their tumorigenicity when injected into immunodeficient animals. Symplekin downregulation also was found to alter ion transport through TJs, to promote the localization of ZONAB in the membrane rather than the nucleus, and strongly to enhance cell polarization in a 3D matrix, leading to the formation of spheroids organized around a central lumen. Claudin-2 expression was reduced following symplekin down-regulation, an effect mimicked when ZONAB expression was down-regulated using selective siRNA. Virus-mediated restoration of claudin-2 expression was found to restore nuclear expression of ZONAB in HT29ΔSym cells and to rescue the phenotypic alterations induced by symplekin down-regulation of cell polarity, paracellular transport, ZONAB localization, cyclin D1 expression, proliferation, and anchorage-independent growth. Finally, siRNA-mediated claudin-2 down-regulation increased the transepithelial resistance and decreased cyclin D1 expression and ZONAB nuclear localization, similar to observations in symplekindepleted cells. Our results suggest that nuclear overexpression of symplekin promotes tumorigenesis in the human colon and that the regulation of claudin-2 expression is instrumental in this effect.polarity | transcription | tumorigenesis | colorectal | tight junctions

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Section: Discussionmentioning

confidence: 99%

Symplekin promotes tumorigenicity by up-regulating claudin-2 expression

Büchert

Papin

Bonnans

et al. 2010

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

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“…Similarly, several junctional scaffolding proteins are bound and inactivated by viral oncogenes (Glaunsinger et al, 2001;Latorre et al, 2005). By contrast, ZONAB and its activating protein Apg2 are both upregulated in hepatocellular carcinomas, which suggests that this proliferationpromoting pathway is stimulated (Arakawa et al, 2004;Gotoh et al, 2004;Hayashi et al, 2002).…”

Section: Tjs In Diseasementioning

confidence: 98%

Tight junctions at a glance

Balda

Matter

2008

Journal of Cell Science

214

168

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“…The transcription of dbpA is positively regulated by E2F1 (2), which is also implicated in hepatocarcinogenesis (3).…”

Section: Introductionmentioning

confidence: 99%

Gene expression profile of DNA binding protein A transgenic mice

Tobita

Kajino²,

Inami³

et al. 2006

Int J Oncol

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Abstract.We recently reported that the expression of dbpA (DNA binding protein A) is associated with advanced stages of human hepatocellular carcinoma (HCC) and that its transcription is positively regulated by E2F1, which is also implicated in hepatocarcinogenesis. To study the in vivo effect of dbpA on hepatocarcinogenesis, we generated the dbpA-transgenic mouse that specifically expressed a transgene in hepatocytes. Here, we studied the effect of dbpA on the expression of other cellular genes by using microarray analyses. The expression profiles from livers of 31-and 32-week-old male transgenic mice [Tg(+)] that did not show any morphological changes and from livers of their male wild-type littermates [Tg(-)] were compared. Expression differences detected by microarray analyses were validated by reverse transcription-polymerase chain reaction (RT-PCR) using total RNA samples from livers of 3 pairs of Tg(+) and (-) mice. The 11 up-regulated genes included 7 carcinogenesis-related genes (Igfbp1, Tff3, Hpx, Orm2, Ctsl, Plg, Jdp1), and the 9 down-regulated genes included Car3 that is associated with the protection of cells from attack by oxygen radicals. We confirmed that the expression of Igfbp1 (insulin like growth factor binding protein 1) was reduced by siRNA targeting dbpA in the human HCC cell line. In conclusion, our present data suggested that dbpA could be positively involved in carcinogenesis by changing the expression profiles of cellular genes.

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Transcription of dbpA, a Y box binding protein, is positively regulated by E2F1: implications in hepatocarcinogenesis

Cited by 37 publications

References 31 publications

Symplekin promotes tumorigenicity by up-regulating claudin-2 expression

Symplekin promotes tumorigenicity by up-regulating claudin-2 expression

Tight junctions at a glance

Gene expression profile of DNA binding protein A transgenic mice

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