PAX2 Expression in Ovarian Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2013 Mar 19

PMID 23502471

Citations 19

Authors

Huijuan Song

Suet-Yan Kwan

Daisy I Izaguirre

Zhifei Zu

Yvonne T Tsang

Celestine S Tung

Erin R King

Samuel C Mok

David M Gershenson

Kwong-Kwok Wong

Affiliations

Soon will be listed here.

Abstract

PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two ovarian cancer cell lines: RMUGL (mucinous) and TOV21G (clear cell), with high PAX2 expression were chosen for further study. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, protein profiles, and gene expression profiles. The result indicated that these stable PAX2 knockdown cells had reduced cell proliferation and migration. Microarray analysis indicated that several genes involved in growth inhibition and motility, such as G0S2, GREM1, and WFDC1, were up-regulated in PAX2 knockdown cells. On the other hand, over-expressing PAX2 in PAX2-negative ovarian cell lines suppressed their cell proliferation. In summary, PAX2 could have both oncogenic and tumor suppression functions, which might depend on the genetic content of the ovarian cancer cells. Further investigation of PAX2 in tumor suppression and mortality is warranty.

Citing Articles

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References

Khoubehi B, Kessling A, Adshead J, Smith G, Smith R, Ogden C . Expression of the developmental and oncogenic PAX2 gene in human prostate cancer. J Urol. 2001; 165(6 Pt 1):2115-20. DOI: 10.1097/00005392-200106000-00080. View

Wiegand K, Shah S, Al-Agha O, Zhao Y, Tse K, Zeng T . ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med. 2010; 363(16):1532-43. PMC: 2976679. DOI: 10.1056/NEJMoa1008433. View

Dressler G, Woolf A . Pax2 in development and renal disease. Int J Dev Biol. 1999; 43(5):463-8. View

Welch C, Santra M, El-Assaad W, Zhu X, Huber W, Keys R . Identification of a protein, G0S2, that lacks Bcl-2 homology domains and interacts with and antagonizes Bcl-2. Cancer Res. 2009; 69(17):6782-9. PMC: 2841785. DOI: 10.1158/0008-5472.CAN-09-0128. View

Chan-Ling T, Chu Y, Baxter L, Weible Ii M, Hughes S . In vivo characterization of astrocyte precursor cells (APCs) and astrocytes in developing rat retinae: differentiation, proliferation, and apoptosis. Glia. 2008; 57(1):39-53. DOI: 10.1002/glia.20733. View

Zhang Z, Huang L, Zhao W, Rigas B . Annexin 1 induced by anti-inflammatory drugs binds to NF-kappaB and inhibits its activation: anticancer effects in vitro and in vivo. Cancer Res. 2010; 70(6):2379-88. PMC: 2953961. DOI: 10.1158/0008-5472.CAN-09-4204. View

Weber S, Taylor J, Winyard P, Baker K, Sullivan-Brown J, Schild R . SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol. 2008; 19(5):891-903. PMC: 2386720. DOI: 10.1681/ASN.2006111282. View

Gokden N, Kemp S, Gokden M . The utility of Pax-2 as an immunohistochemical marker for renal cell carcinoma in cytopathology. Diagn Cytopathol. 2008; 36(7):473-7. DOI: 10.1002/dc.20842. View

Monte N, Webster K, Neuberg D, Dressler G, Mutter G . Joint loss of PAX2 and PTEN expression in endometrial precancers and cancer. Cancer Res. 2010; 70(15):6225-32. PMC: 2912978. DOI: 10.1158/0008-5472.CAN-10-0149. View

10.

Abdel-Hakeem A, Henry T, Magee T, Desai M, Ross M, Mansano R . Mechanisms of impaired nephrogenesis with fetal growth restriction: altered renal transcription and growth factor expression. Am J Obstet Gynecol. 2008; 199(3):252.e1-7. PMC: 2932650. DOI: 10.1016/j.ajog.2008.05.018. View

11.

Chen E, Mehra K, Mehrad M, Ning G, Miron A, Mutter G . Secretory cell outgrowth, PAX2 and serous carcinogenesis in the Fallopian tube. J Pathol. 2010; 222(1):110-6. PMC: 2914810. DOI: 10.1002/path.2739. View

12.

Fletcher J, Hu M, Berman Y, Collins F, Grigg J, McIver M . Multicystic dysplastic kidney and variable phenotype in a family with a novel deletion mutation of PAX2. J Am Soc Nephrol. 2005; 16(9):2754-61. DOI: 10.1681/ASN.2005030239. View

13.

Gnarra J, Dressler G . Expression of Pax-2 in human renal cell carcinoma and growth inhibition by antisense oligonucleotides. Cancer Res. 1995; 55(18):4092-8. View

14.

Ritz-Laser B, Estreicher A, Gauthier B, Philippe J . The paired homeodomain transcription factor Pax-2 is expressed in the endocrine pancreas and transactivates the glucagon gene promoter. J Biol Chem. 2000; 275(42):32708-15. DOI: 10.1074/jbc.M005704200. View

15.

Park D, Yeo S, Wilson M, Yerbury J, Kwong J, Welch W . Clusterin interacts with Paclitaxel and confer Paclitaxel resistance in ovarian cancer. Neoplasia. 2008; 10(9):964-72. PMC: 2517641. DOI: 10.1593/neo.08604. View

16.

Tong G, Chiriboga L, Hamele-Bena D, Borczuk A . Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?. Mod Pathol. 2007; 20(8):856-63. DOI: 10.1038/modpathol.3800827. View

17.

Hueber P, Iglesias D, Chu L, Eccles M, Goodyer P . In vivo validation of PAX2 as a target for renal cancer therapy. Cancer Lett. 2008; 265(1):148-55. DOI: 10.1016/j.canlet.2008.02.016. View

18.

Roh M, Yassin Y, Miron A, Mehra K, Mehrad M, Monte N . High-grade fimbrial-ovarian carcinomas are unified by altered p53, PTEN and PAX2 expression. Mod Pathol. 2010; 23(10):1316-24. DOI: 10.1038/modpathol.2010.119. View

19.

Silberstein G, Dressler G, Van Horn K . Expression of the PAX2 oncogene in human breast cancer and its role in progesterone-dependent mammary growth. Oncogene. 2002; 21(7):1009-16. DOI: 10.1038/sj.onc.1205172. View

20.

Hsu D, Economides A, Wang X, Eimon P, Harland R . The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Mol Cell. 1998; 1(5):673-83. DOI: 10.1016/s1097-2765(00)80067-2. View