Artigo Revisado por pares

EXPRESSION OF THE DEVELOPMENTAL AND ONCOGENIC PAX2 GENE IN HUMAN PROSTATE CANCER

2001; Lippincott Williams & Wilkins; Volume: 165; Issue: 6 Part 1 Linguagem: Inglês

10.1016/s0022-5347(05)66304-5

ISSN

1527-3792

Autores

Bijan Khoubehi, Anna M. Kessling, James Adshead, Gillian L. Smith, Daron Smith, Christopher Ogden,

Tópico(s)

Renal cell carcinoma treatment

Resumo

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Jun 2001EXPRESSION OF THE DEVELOPMENTAL AND ONCOGENIC PAX2 GENE IN HUMAN PROSTATE CANCER BIJAN KHOUBEHI, ANNA M. KESSLING, JAMES M. ADSHEAD, GILLIAN L. SMITH, RICHARD D. SMITH, and CHRISTOPHER W. OGDEN BIJAN KHOUBEHIBIJAN KHOUBEHI , ANNA M. KESSLINGANNA M. KESSLING , JAMES M. ADSHEADJAMES M. ADSHEAD , GILLIAN L. SMITHGILLIAN L. SMITH , RICHARD D. SMITHRICHARD D. SMITH , and CHRISTOPHER W. OGDENCHRISTOPHER W. OGDEN View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)66304-5AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: In the human prostate cancer cell lines LNCaP, DU145 and PC3, 27 primary prostate cancers, 10 benign prostatic hyperplasia specimens and 5 normal prostates we investigated the expression pattern of PAX2, a member of the PAX family of developmental control genes. PAX2 is expressed at high levels in developing undifferentiated cells of the urogenital system and is repressed upon terminal differentiation with no expression in normal adult cells. It is also been shown to be a proto-oncogene in mice and is expressed in human renal cell carcinoma. Materials and Methods: PAX2 expression was assessed at the RNA level by reverse transcriptase-polymerase chain reaction and Southern blot analysis using specific sets of nucleotides. The expression pattern of PAX2 was reconfirmed at the protein level by immunofluorescence in the cell lines, and by Western blot analysis in primary human prostate cancers and benign prostatic tissue. Results: Using reverse transcription-polymerase chain reaction combined with Southern hybridization PAX2 expression was detected in 52% of primary cancers and all 3 cell lines. PAX2 expression in these samples was confirmed at a protein level using immunoblotting and immunofluorescence. PAX2 messenger RNA was not detected in any benign or normal prostatic samples. Immunoblotting of protein from benign prostatic hyperplasia samples confirmed the lack of expression of PAX2 protein. Conclusions: The expression of PAX2 in prostate cancer compared to nonmalignant prostates is statistically significant (Fisher's exact test p = 0.0004). These results suggest a possible role for PAX2 in prostate cancer. Although previous studies have suggested a role for PAX2 for supporting proliferation in undifferentiated cells, no correlation of PAX2 expression with Gleason score was found in prostate cancer. References 1 : Cancer statistics, 1998. CA Cancer J Clin1998; 48: 6. Google Scholar 2 : Differential Diagnosis of Prostate Disorders. Hampshire: Gower Medical Pub.1993: 38. Google Scholar 3 : Genetic basis and clonal evolution of human prostate cancer. Adv Cancer Res1996; 68: 225. Google Scholar 4 : PAX genes: what's new in developmental biology and cancer?. Hum Mol Genet1995; 4: 1717. Google Scholar 5 : Chromosomal translocations in human cancer. Nature1994; 372: 143. Google Scholar 6 : Pax in development. Cell1992; 69: 719. Google Scholar 7 : Mammalian Pax genes. Annu Rev Genet1994; 28: 219. Google Scholar 8 : Emerging roles for PAX transcription factors in cancer biology. Gen Physiol Biophys1998; 17: 211. Google Scholar 9 : Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system. Development1990; 109: 787. Google Scholar 10 : Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities. Nature1993; 362: 65. Google Scholar 11 : Pax-2 controls multiple steps of urogenital development. Development1995; 121: 4057. Google Scholar 12 : Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux. Nat Genet1995; 9: 358. Google Scholar 13 : The oncogenic potential of Pax genes. EMBO J1993; 12: 2361. Google Scholar 14 : Pax-2 is a DNA-binding protein expressed in embryonic kidney and Wilms tumor. Proc Natl Acad Sci USA1992; 89: 1179. Google Scholar 15 : Expression of Pax-2 in human renal cell carcinoma and growth inhibition by antisense oligonucleotides. Cancer Res1995; 55: 4092. Google Scholar 16 : Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet1993; 5: 230. Google Scholar 17 : Expression of PAX3 in Ewing's sarcoma family of tumors. Biochem Mol Med1997; 60: 121. Google Scholar 18 : Deregulated expression of PAX5 in medulloblastoma. Proc Natl Acad Sci USA1995; 92: 5709. Google Scholar 19 : PAX5 expression correlates with increasing malignancy in human astrocytomas. Clin Cancer Res1995; 1: 207. Google Scholar 20 : The expression of PAX5 in human transitional cell carcinoma of the bladder: relationship with de-differentiation. Br J Urol1999; 83: 1039. Google Scholar 21 : PAX8, a human paired box gene: isolation and expression in developing thyroid, kidney and Wilms' tumors. Development1992; 116: 611. Google Scholar 22 : Expression of thyroid-specific transcription factors TTF-1 and PAX-8 in human thyroid neoplasms. Cancer Res1994; 54: 4744. Google Scholar 23 : Fusion genes resulting from alternative chromosomal translocations are overexpressed by gene-specific mechanisms in alveolar rhabdomyosarcoma. Proc Natl Acad Sci USA1997; 94: 8047. Google Scholar 24 : Localisation of a 10q breakpoint within the PAX2 gene in a patient with a de novo t(10;13) translocation and optic nerve coloboma-renal disease. J Med Genet1997; 34: 213. Google Scholar 25 : Chromosomal clues to the development of prostate tumors. Prostate1999; 38: 303. Google Scholar 26 : Prostatectomy tissue for research, balancing patient care and discovery. Am J Clin Pathol1998; 110: 4. Google Scholar 27 : The PAX2 transcription factor is expressed in cystic and hyperproliferative dysplastic epithelia in human kidney malformations. J Clin Invest1996; 98: 451. Google Scholar 28 : Mutation of the MXI1 gene in prostate cancer. Nat Genet1995; 9: 249. Google Scholar 29 : PTEN/MMAC1/TEP1 involvement in primary prostate cancers. Oncogene1998; 16: 2879. Google Scholar 30 : Role of mesenchymal-epithelial interactions in normal and abnormal development of male urogenital glands. In: Ultrastructure of Male Urogenital Glands: Prostate, Seminal Vesicle, Urethra and Bulbourethral Glands. Boston: Kluwer Academic Pub.1994: 25. Google Scholar 31 : The oncogenic potential of Pax genes. EMBO J1993; 12: 2361. Google Scholar 32 : Repression of Pax-2 by WT1 during normal kidney development. Development1995; 121: 867. Google Scholar 33 : The paired-box transcription factor, PAX2, positively modulates expression of the Wilms' tumor suppressor gene (WT1). Oncogene1996; 13: 447. Google Scholar 34 : Loss of p53 function through PAX-mediated transcriptional repression. EMBO J1995; 14: 5638. Google Scholar 35 : An uncertain role for p53 gene alterations in human prostate cancers. Cancer Res1996; 56: 3814. Google Scholar 36 : PAX: developmental control genes in cell growth and differentiation. Cell Growth Differ1996; 7: 405. Google Scholar 37 : Differentially expressed genes in activin-induced apoptotic LNCaP cells. Biochem Biophys Res Commun1999; 257: 187. Google Scholar From the Academic Unit of Medical and Community Genetics, Imperial College of Science Technology and Medicine, Kennedy-Galton Centre and Department of Urology, Northwick Park Hospital, Northwest London Hospitals National Health Service Trust, London, United Kingdom© 2001 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 165Issue 6 Part 1June 2001Page: 2115-2120 Advertisement Copyright & Permissions© 2001 by American Urological Association, Inc.Keywordsprostategenes, structuralgene expressionprostatic neoplasmsMetricsAuthor Information BIJAN KHOUBEHI More articles by this author ANNA M. KESSLING Supported by the NHS executive (R&D). More articles by this author JAMES M. ADSHEAD More articles by this author GILLIAN L. SMITH More articles by this author RICHARD D. SMITH More articles by this author CHRISTOPHER W. OGDEN More articles by this author Expand All Advertisement PDF downloadLoading ...

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