Expression of the Developmental and Oncogenic Pax2 Gene in Human Prostate Cancer

Khoubehi, Bijan; Kessling, Anna M.; Adshead, James; Smith, Gardner W.; Smith, Richard; Ogden, Christopher

doi:10.1097/00005392-200106000-00080

Cited by 19 publications

(19 citation statements)

References 27 publications

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“…Indeed, AngII (10 Ϫ9 M) upregulated Pax-2 in MK4 cells ( Figure 1A) but did not induce Pax-2 in MK3 cells ( Figure 1B). Immunostaining seemed intranuclear, consistent with the fact that Pax-2 is a nuclear transcription factor (22,24).…”

Section: Pax-2 Is Visualized In Mk4 But Not Mk3 Cellssupporting

confidence: 68%

“…Aliquots of total RNA (2 g) were used for cDNA synthesis (SuperScript preamplification system; Invitrogen). Subsequently, 2 l of the cDNA reaction mixture was taken to amplify Pax-2 and ␤-actin cDNA fragments using the forward primer 5'-TTTGTGAACGGCCG-GCCCCTA-3' and the reverse primer 5'-CATTGTCACAGATGC-CCTCGG-3', corresponding to the nucleotide sequences n ϩ 622 to n ϩ 642 and n ϩ 902 to n ϩ 922 of Pax-2 cDNA (22). Primers specific for rat ␤-actin (23) (forward and reverse primers 5'-ATGCCATCCT-GCGTCTGGACCTGGC-3' and 5'-AGCATTTGCGGTGCACGAT-GGAGGG-3', corresponding to the nucleotide sequences n ϩ 155 to n ϩ 179 of exon 3 and n ϩ 115 to n ϩ 139 of exon 5 of rat ␤-actin) were used as internal controls.…”

Section: Reverse Transcription-pcr For Pax-2 Mrnamentioning

confidence: 99%

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Angiotensin II Increases Pax-2 Expression in Fetal Kidney Cells Via the AT2 Receptor

Zhang

Moini

Ingelfinger

2004

Journal of the American Society of Nephrology

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Abstract. Although both the renin angiotensin system (RAS) and the paired homeobox 2 gene (Pax-2) seem critically important in renal organogenesis, whether and how they might interact has not been addressed. The present study asked whether a link between the RAS and Pax-2 exists in fetal renal cells, speculating that such an interaction, if present, might influence renal development. Embryonic kidney explants and embryonic renal cells (mouse late embryonic mesenchymal epithelial cells [MK4] and mouse early embryonic mesenchymal fibroblasts [MK3]) were used. Pax-2 protein and Pax-2 mRNA were detected by immunofluorescence, Western blot, reverse transcription-PCR, and real-time PCR. Angiotensin II (AngII) upregulated Pax-2 protein and Pax-2 mRNA expression via the AngII type 2 (AT 2 ) receptor in MK4 but not in MK3 cells. The stimulatory effect of AngII on Pax-2 gene expression could be blocked by PD123319 (AT 2 inhibitor), AG 490 (a specific Janus kinase 2 inhibitor), and genistein (a tyrosine kinase inhibitor) but not by losartan (AT 1 inhibitor), SB203580 (specific p38 mitogen-activated protein kinase inhibitor), PD98059 (specific MEK inhibitor), SP600125 (JNK inhibitor), and diphenyleneiodonium chloride (an NADPH oxidase inhibitor). Moreover, embryonic kidney explants in culture confirmed that AngII upregulates Pax-2 gene expression via the AT 2 receptor. These studies demonstrate that the stimulatory effect of AngII on Pax-2 gene expression is mediated, at least in part, via the Janus kinase 2/signal transducers and activators of transcription signaling transduction pathway, suggesting that RAS and Pax-2 interactions may be important in renal development.Renal morphogenesis involves complex events in which many genes interact. When the normal pattern of nephrogenesis is interrupted, renal abnormalities ensue. More than 40 genes have been reported to participate in renal development, including glial cell line-derived neurotropic factor, RET, Pax-2, Wilms' tumor suppressor gene, N-Myc, and several components of the renin-angiotensin system (RAS) (1). However, how these putative regulatory factors function and interact to control nephrogenesis is incompletely delineated.The intrarenal RAS (2-4) seems to play a major role in renal development and repair (5,6). Woods et al. (7,8) showed that the intrarenal RAS is downregulated during the perinatal period in offspring of mothers who are subjected to moderate protein restriction during gestation. Such data suggest that during the perinatal period, angiotensin II (AngII), acting via its receptors, might play an important role in renal development and the long-term control of renal function and arterial pressure (5-8). The importance of the RAS in renal development has also been demonstrated when the RAS is interrupted by inadvertent use of angiotensin-converting enzyme inhibitors in humans (9) or by creating "knockouts" of RAS genes in mice (10).Paired homeobox genes are important in embryogenesis.

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Section: Pax-2 Is Visualized In Mk4 But Not Mk3 Cellssupporting

confidence: 68%

Section: Reverse Transcription-pcr For Pax-2 Mrnamentioning

confidence: 99%

Angiotensin II Increases Pax-2 Expression in Fetal Kidney Cells Via the AT2 Receptor

Zhang

Moini

Ingelfinger

2004

Journal of the American Society of Nephrology

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“…24,25 For example, overexpression of HOXC6, PAX2, and BP1 have been described in PCa. [26][27][28] We have previously shown that methylation of homeobox genes is a common event in PCa, 14 whereas others have shown similar results in so-called methylation 'hot spots' within HOX loci. 29,30 In particular, we demonstrated methylation of the HOXD3 region in primary PCa and that this methylation leads to gene silencing in DU-145 cells.…”

Section: Discussionmentioning

confidence: 95%

DNA methylation of HOXD3 as a marker of prostate cancer progression

Kron

Liu

Pethe

et al. 2010

Laboratory Investigation

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DNA methylation in gene promoters causes gene silencing and is a common event in cancer development and progression. The ability of aberrant methylation events to serve as diagnostic and prognostic markers is being appreciated for many cancers, including prostate cancer. Using quantitative MethyLight technology, we evaluated the relationship between HOXD3 methylation and clinicopathological parameters including biochemical recurrence, pathological stage, Gleason score (GS), and Gleason pattern in a series of 232 radical prostatectomies performed between 1998 and 2001. HOXD3 methylation was significantly greater in GS 7 cancers vs GSr6 cancers (P-value o0.001) as well as pT3/pT4 vs pT2 cancers (P-value o0.001). The proportion of cases with high methylation in GS 7 vs rGS 6 and pT3/pT4 vs pT2 were also significantly different (P-values ¼ 0.002 and 0.005, respectively). There were also significant increases in methylation from Gleason pattern 2-3 and from pattern 3 to 4/5 (paired t-test P-values ¼ 0.01 and o0.001, respectively), whereas methylation from lymph node metastases was decreased when compared with matched tumor tissue (P-value ¼ 0.029). HOXD3 methylation was associated with biochemical recurrence in univariate analysis (P-value ¼ 0.043) and showed evidence for interaction with pathological stage as a predictor variable in Cox regression analysis (P-value ¼ 0.028). The results indicate that HOXD3 methylation distinguishes low-grade prostate cancers from intermediate and high-grade ones and may also have prognostic value when considered together with pathological stage.

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“…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

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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.

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Expression of the Developmental and Oncogenic Pax2 Gene in Human Prostate Cancer

Cited by 19 publications

References 27 publications

Angiotensin II Increases Pax-2 Expression in Fetal Kidney Cells Via the AT2 Receptor

Angiotensin II Increases Pax-2 Expression in Fetal Kidney Cells Via the AT2 Receptor

DNA methylation of HOXD3 as a marker of prostate cancer progression

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

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