Paired-Box genes are frequently expressed in cancer and often required for cancer cell survival

Muratovska, Aleksandra; Zhou, Chaoming; He, Shuji; Goodyer, Paul; Eccles, Michael R.

doi:10.1038/sj.onc.1206766

Cited by 221 publications

(228 citation statements)

References 45 publications

Supporting

Mentioning

214

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, PAX2 was also detected in these two ER-positive peritoneal mesotheliomas, but not in the PR-positive case in which the patient was a teenage girl. Whether this was due to aberrant expression of PAX2 [40][41][42] in malignant tumors, or Mü llerian metaplastic transformation of malignant mesotheliomas, 43,44 is under further investigation. Nevertheless, PAX2 might be useful as an additional immunohistochemical marker in the differential diagnosis of papillary serous carcinomas of the ovary and female malignant mesotheliomas of the peritoneum, with moderate sensitivity (67%) and specificity (88%).…”

Section: Discussionmentioning

confidence: 99%

Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?

et al. 2007

View full text Add to dashboard Cite

PAX2 is a urogenital developmental transcription factor expressed in the Wolffian ducts, developing kidneys, and Mü llerian ducts during embryonic stage. Its function in renal development is well documented and its clinical application in the diagnosis of lesions of renal origin has been reported recently. However, information on its role in the Mü llerian-derived genital tract is sparse. In this study, we investigated the expression of PAX2 in human female genital tract using immunohistochemistry. We demonstrated that PAX2 was expressed specifically in the epithelial cells of fallopian tube, endometrial and endocervical glands, but not in the stromal tissues in these areas. PAX2 was detected in secondary Mü llerian structures in the ovary, such as endometriotic and endosalpingiotic glands and rete ovarii, but not in ovarian surface epithelium, surface epithelium-derived inclusion cysts, stroma, or sex-cord-derived structures such as follicles, oocytes, and corpus luteum. In addition, PAX2 was detected in 67% of ovarian papillary serous carcinomas (N ¼ 36) but rarely in peritoneal malignant mesotheliomas, with two exceptions (N ¼ 54). Interestingly, the two PAX2-positive 'peritoneal malignant mesotheliomas' were from female patients and were positive for estrogen receptor. The significance of expression of PAX2 and estrogen receptor in these cases is under investigation. Taken together, we suggest that PAX2 is a novel Mü llerian-specific epithelial marker when used in proper clinical settings. Identification of PAX2 in the majority of papillary serous carcinomas of the ovary but not in the ovarian surface epithelium or epithelium-derived inclusion cysts suggests that this malignant epithelial tumor may be directly derived from the primary or secondary Mü llerian epithelium in or surrounding the ovary, rather than from the surface epithelium or its derivatives.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Primers used to amplify c-Myc (63), PAX2, and β2-microglobulin (B2M; ref. 27) were described previously. Relative expression of mRNA transcripts was calculated with respect to B2M transcript levels.…”

Section: Reverse Transcription-pcr and Quantitative Real-time Pcrmentioning

confidence: 99%

“…Expression of PAX genes in cancer correlates with reduced apoptosis as well as increased proliferative and invasive phenotypes (26)(27)(28)(29). Inhibition of PAX2 in renal cell lines reduces proliferation as well as resistance to cisplatin treatment (26,28).…”

Section: Introductionmentioning

confidence: 99%

Calcineurin A–Binding Protein, a Novel Modulator of the Calcineurin-Nuclear Factor of Activated T-Cell Signaling Pathway, Is Overexpressed in Wilms' Tumors and Promotes Cell Migration

Nguyen

Béland²,

Gaitan³

et al. 2009

Molecular Cancer Research

View full text Add to dashboard Cite

Current therapeutic strategies against Wilms' tumor (WT) reach 80% to 85% success rate. In spite of this, a remaining 15% to 20% of tumors relapse and are associated with increased metastasis and poor prognosis. To identify new regulators of WT progression, we screened for developmental target genes of Pax2, a key regulator of kidney development and a WT signature gene. We show that one of these target genes, calcineurin A-binding protein (CnABP), is coexpressed with Pax2 during kidney development and is overexpressed in >70% of WT samples analyzed. The CnABP gene encodes a novel protein product conserved in higher vertebrates. We show that CnABP promotes cell proliferation and migration in cell culture experiments. Biochemical analyses additionally identified an interaction between CnABP and calcineurin Aβ, the catalytic subunit of the calcium-responsive serine/ threonine phosphatase calcineurin. We show that this interaction leads to the inhibition of calcineurin phosphatase activity and prevents nuclear factor of activated T-cell (NFAT) nuclear translocation. Inhibition of NFAT nuclear localization results in decreased NFAT transcriptional response. Together, these data identify a new modulator of calcineurin signaling up-regulated in WTs. (Mol Cancer Res 2009;7(6):821-31)

show abstract

“…1 FOX and PAX transcription factors play an important role in various cancers affecting cell differentiation, cell cycle control and apoptosis. [14][15][16][17][18][19] LMO2 represents an important bridging molecule of regulatory multiprotein complexes known to affect cell transcription and differentiation in various tumors. 20 As a consequence of these findings, we examined the potential of RBP2-H1/JARID1B to influence gene transcription, either alone or in combination with FOXG1b/PAX9/LMO2, using a luciferase reporter gene model and genome-wide gene regulation approaches.…”

mentioning

confidence: 99%

RBP2‐H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells

Roesch

Mueller²,

Stempfl

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

The RBP2-H1/JARID1B nuclear protein belongs to the ARID family of DNA-binding proteins and is a potential tumor suppressor that is lost during melanoma development. As we have recently shown, one physiological function of RBP2-H1/JARID1B is to exert cell cycle control via maintenance of active retinoblastoma protein. We now add new evidence that RBP2-H1/JARID1B can also directly regulate gene transcription in a reporter assay system, either alone or as part of a multimolecular complex together with the developmental transcription factors FOXG1b and PAX9. In melanoma cells, chromatin immunoprecipitation combined with promoter chip analysis (ChIP-on-chip) suggests a direct binding of re-expressed RBP2-H1/JARID1B to a multitude of human regulatory chromosomal elements (promoters, enhancers and introns). Among those, a set of 23 genes, including the melanoma relevant genes CDK6 and JAG-1 could be confirmed by cDNA microarray analyses to be differentially expressed after RBP2-H1/JARID1B re-expression. In contrast, in nonmelanoma HEK 293 cells, RBP2-H1/JARID1B overexpression only evokes a minor transcriptional response in cDNA microarray analyses. Because the transcriptional regulation in melanoma cells is accompanied by an inhibition of proliferation, an increase in caspase activity and a partial cell cycle arrest in G1/0, our data support an anti-tumorigenic role of RBP2-H1/JARID1B in melanocytic cells. ' 2007 Wiley-Liss, Inc.Key words: melanoma; transcription; gene expression; retinoblastoma protein binding protein; apoptosisIn 1999, our group detected a gene transcript suppressed by UV-B in normal human melanocytes (Acc. No. AF087481, 1 ). Based on its homology to the previously described RBP2, 2 this new gene was termed retinoblastoma binding protein 2-homolog 1 (RBP2-H1). Subsequent expression studies revealed a frequent loss of RBP2-H1 in the majority of advanced and metastatic melanomas in vivo and in many melanoma cell lines, whereas benign melanocytic tumors, normal tissues and other cancer types mostly retain RBP2-H1. 1,3 Recently, we showed that RBP2-H1 has a tumor suppressive activity partly due to binding and stabilization of hypophosphorylated retinoblastoma protein (pRb) leading to maintenance of pRb-mediated cell cycle control. 4 As a result of truncation studies, we located the pRb-binding activity of RBP2-H1 to its C-term, containing a homolog region of the non-T/E1A-pRb binding domain known from other retinoblastoma binding proteins like RBP2. 5 Moreover, RBP2-H1 and its splicing variants PLU-1 and RBBP2H1a contain further well-conserved domains known to be involved in direct gene regulation and chromatin homeostasis, e.g. 3 PHD motifs and the ARID (AT-rich interacting) DNA-binding domain. [6][7][8][9] Although the 3 splicing variants show a cDNA sequence homology of more than 98%, RBP2-H1 differs from PLU-1 and RBBP2H1a by an additional exon encoding a region with strong homology to chromosomal ALU repeats. Thus, previously reported differences in tissue expression (PLU-1 shows a restricted expre...

show abstract

Paired-Box genes are frequently expressed in cancer and often required for cancer cell survival

Cited by 221 publications

References 45 publications

Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?

Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?

Calcineurin A–Binding Protein, a Novel Modulator of the Calcineurin-Nuclear Factor of Activated T-Cell Signaling Pathway, Is Overexpressed in Wilms' Tumors and Promotes Cell Migration

RBP2‐H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells

Contact Info

Product

Resources

About