Skip to main content
Erschienen in: Medical Oncology 3/2015

01.03.2015 | Original Paper

Downregulation of UPK1A suppresses proliferation and enhances apoptosis of bladder transitional cell carcinoma cells

verfasst von: Haiyan Zhu, Yuxin Tang, Xiangyang Zhang, Xianzhen Jiang, Yong Wang, Yu Gan, Jianfu Yang

Erschienen in: Medical Oncology | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

Uroplakin 1A (UPK1A) is a specific marker of mammalian urothelium and one of major proteins contained in urothelial plaques. Many recent studies reported that UPK1A could be useful marker for diagnosis, detection and prognostic prediction of transitional cell carcinoma. However, relatively little is known about its exact roles in bladder transitional cell carcinoma (BTCC). We tried to explore the roles UPK1A plays in BTCC via the transfection of its antisense nucleotides (AS) into T24 cells to observe their changes of proliferation and apoptosis. After AS was successfully transfected into T24 cells, the percentages of proliferating T24 cells at 24 and 48 h after the treatment were 57.2 ± 6.8 and 44.7 ± 5.2 %, significantly lower than that of control group, as shown by MTT (p < 0.05 and 0.01). At 24 h after transfection of AS, the percentage of apoptotic T24 cells was 26.87 % measured by flow cytometry, significantly higher than that of control group (p < 0.01). Similarly, Hoechst 33258 staining showed that the percentage of apoptotic nuclei of T24 cells after 24 h treated by AS was 28.9 %, significantly higher than that of control (p < 0.05). The most common and typical morphological changes of apoptosis, including shrink, pyknosis and karyorrhexis of T24 cells nuclei and DNA fragmentation were seen from Hoechst 33258 staining and DNA agarose gel electrophoresis. Taken together, inhibition of UPK1A can suppress proliferation and enhance apoptosis of BTCC T24 cells, suggesting it a potential target to treat this disease.
Literatur
2.
Zurück zum Zitat Jung I, Messing E. Molecular mechanisms and pathways in bladder cancer development and progression. Cancer Control J Moffitt Cancer Center. 2000;7(4):325–34. Jung I, Messing E. Molecular mechanisms and pathways in bladder cancer development and progression. Cancer Control J Moffitt Cancer Center. 2000;7(4):325–34.
3.
Zurück zum Zitat Holmang S, Hedelin H, Anderstrom C, Johansson SL. The relationship among multiple recurrences, progression and prognosis of patients with stages Ta and T1 transitional cell cancer of the bladder followed for at least 20 years. J Urol. 1995;153(6):1823–6 (discussion 6–7).CrossRefPubMed Holmang S, Hedelin H, Anderstrom C, Johansson SL. The relationship among multiple recurrences, progression and prognosis of patients with stages Ta and T1 transitional cell cancer of the bladder followed for at least 20 years. J Urol. 1995;153(6):1823–6 (discussion 6–7).CrossRefPubMed
4.
Zurück zum Zitat Pawinski A, Sylvester R, Kurth KH, Bouffioux C, van der Meijden A, Parmar MK et al. A combined analysis of European Organization for Research and Treatment of Cancer, and Medical Research Council randomized clinical trials for the prophylactic treatment of stage TaT1 bladder cancer. European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council Working Party on Superficial Bladder Cancer. J Urol. 1996;156(6):1934–40, (discussion 40–41). Pawinski A, Sylvester R, Kurth KH, Bouffioux C, van der Meijden A, Parmar MK et al. A combined analysis of European Organization for Research and Treatment of Cancer, and Medical Research Council randomized clinical trials for the prophylactic treatment of stage TaT1 bladder cancer. European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council Working Party on Superficial Bladder Cancer. J Urol. 1996;156(6):1934–40, (discussion 40–41).
9.
Zurück zum Zitat Sun TT, Liang FX, Wu XR. Uroplakins as markers of urothelial differentiation. Adv Exp Med Biol. 1999;462:7–18 (discussion 103–114).CrossRefPubMed Sun TT, Liang FX, Wu XR. Uroplakins as markers of urothelial differentiation. Adv Exp Med Biol. 1999;462:7–18 (discussion 103–114).CrossRefPubMed
10.
Zurück zum Zitat Olsburgh J, Harnden P, Weeks R, Smith B, Joyce A, Hall G, et al. Uroplakin gene expression in normal human tissues and locally advanced bladder cancer. J Pathol. 2003;199(1):41–9. doi:10.1002/path.1252.CrossRefPubMed Olsburgh J, Harnden P, Weeks R, Smith B, Joyce A, Hall G, et al. Uroplakin gene expression in normal human tissues and locally advanced bladder cancer. J Pathol. 2003;199(1):41–9. doi:10.​1002/​path.​1252.CrossRefPubMed
11.
Zurück zum Zitat Li SM, Zhang ZT, Chan S, McLenan O, Dixon C, Taneja S, et al. Detection of circulating uroplakin-positive cells in patients with transitional cell carcinoma of the bladder. J Urol. 1999;162(3 Pt 1):931–5.CrossRefPubMed Li SM, Zhang ZT, Chan S, McLenan O, Dixon C, Taneja S, et al. Detection of circulating uroplakin-positive cells in patients with transitional cell carcinoma of the bladder. J Urol. 1999;162(3 Pt 1):931–5.CrossRefPubMed
12.
Zurück zum Zitat Wu RL, Osman I, Wu XR, Lu ML, Zhang ZF, Liang FX, et al. Uroplakin II gene is expressed in transitional cell carcinoma but not in bilharzial bladder squamous cell carcinoma: alternative pathways of bladder epithelial differentiation and tumor formation. Cancer Res. 1998;58(6):1291–7.PubMed Wu RL, Osman I, Wu XR, Lu ML, Zhang ZF, Liang FX, et al. Uroplakin II gene is expressed in transitional cell carcinoma but not in bilharzial bladder squamous cell carcinoma: alternative pathways of bladder epithelial differentiation and tumor formation. Cancer Res. 1998;58(6):1291–7.PubMed
13.
Zurück zum Zitat Daniel PT, Sturm I, Ritschel S, Friedrich K, Dorken B, Bendzko P, et al. Detection of genomic DNA fragmentation during apoptosis (DNA ladder) and the simultaneous isolation of RNA from low cell numbers. Anal Biochem. 1999;266(1):110–5. doi:10.1006/abio.1998.2929.CrossRefPubMed Daniel PT, Sturm I, Ritschel S, Friedrich K, Dorken B, Bendzko P, et al. Detection of genomic DNA fragmentation during apoptosis (DNA ladder) and the simultaneous isolation of RNA from low cell numbers. Anal Biochem. 1999;266(1):110–5. doi:10.​1006/​abio.​1998.​2929.CrossRefPubMed
14.
Zurück zum Zitat Kageyama S, Yoshiki T, Isono T, Tanaka T, Kim CJ, Yuasa T, et al. High expression of human uroplakin Ia in urinary bladder transitional cell carcinoma. Jpn J Cancer Res Gann. 2002;93(5):523–31.CrossRefPubMed Kageyama S, Yoshiki T, Isono T, Tanaka T, Kim CJ, Yuasa T, et al. High expression of human uroplakin Ia in urinary bladder transitional cell carcinoma. Jpn J Cancer Res Gann. 2002;93(5):523–31.CrossRefPubMed
15.
Zurück zum Zitat Moll R, Wu XR, Lin JH, Sun TT. Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas. Am J Pathol. 1995;147(5):1383–97.PubMedCentralPubMed Moll R, Wu XR, Lin JH, Sun TT. Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas. Am J Pathol. 1995;147(5):1383–97.PubMedCentralPubMed
16.
Zurück zum Zitat Yuasa T, Yoshiki T, Isono T, Tanaka T, Okada Y. Molecular cloning and expression of uroplakins in transitional cell carcinoma. Adv Exp Med Biol. 2003;539(Pt A):33–46.PubMed Yuasa T, Yoshiki T, Isono T, Tanaka T, Okada Y. Molecular cloning and expression of uroplakins in transitional cell carcinoma. Adv Exp Med Biol. 2003;539(Pt A):33–46.PubMed
17.
Zurück zum Zitat Xu X, Sun TT, Gupta PK, Zhang P, Nasuti JF. Uroplakin as a marker for typing metastatic transitional cell carcinoma on fine-needle aspiration specimens. Cancer. 2001;93(3):216–21.CrossRefPubMed Xu X, Sun TT, Gupta PK, Zhang P, Nasuti JF. Uroplakin as a marker for typing metastatic transitional cell carcinoma on fine-needle aspiration specimens. Cancer. 2001;93(3):216–21.CrossRefPubMed
19.
Zurück zum Zitat Osman I, Kang M, Lee A, Deng FM, Polsky D, Mikhail M, et al. Detection of circulating cancer cells expressing uroplakins and epidermal growth factor receptor in bladder cancer patients. Int J Cancer. 2004;111(6):934–9. doi:10.1002/ijc.20366.CrossRefPubMed Osman I, Kang M, Lee A, Deng FM, Polsky D, Mikhail M, et al. Detection of circulating cancer cells expressing uroplakins and epidermal growth factor receptor in bladder cancer patients. Int J Cancer. 2004;111(6):934–9. doi:10.​1002/​ijc.​20366.CrossRefPubMed
20.
Zurück zum Zitat Yuasa T, Yoshiki T, Isono T, Tanaka T, Hayashida H, Okada Y. Expression of transitional cell-specific genes, uroplakin Ia and II, in bladder cancer: detection of circulating cancer cells in the peripheral blood of metastatic patients. Int J Urol Off J Jpn Urol Assoc. 1999;6(6):286–92. Yuasa T, Yoshiki T, Isono T, Tanaka T, Hayashida H, Okada Y. Expression of transitional cell-specific genes, uroplakin Ia and II, in bladder cancer: detection of circulating cancer cells in the peripheral blood of metastatic patients. Int J Urol Off J Jpn Urol Assoc. 1999;6(6):286–92.
21.
Zurück zum Zitat Wyllie AH. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980;284(5756):555–6.CrossRefPubMed Wyllie AH. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980;284(5756):555–6.CrossRefPubMed
22.
Zurück zum Zitat Slagsvold HH, Marvik OJ, Eidem G, Kristoffersen N, Paulsen RE. Detection of high molecular weight DNA fragments characteristic of early stage apoptosis in cerebellar granule cells exposed to glutamate. Exp Brain Res. 2000;135(2):173–8.CrossRefPubMed Slagsvold HH, Marvik OJ, Eidem G, Kristoffersen N, Paulsen RE. Detection of high molecular weight DNA fragments characteristic of early stage apoptosis in cerebellar granule cells exposed to glutamate. Exp Brain Res. 2000;135(2):173–8.CrossRefPubMed
Metadaten
Titel
Downregulation of UPK1A suppresses proliferation and enhances apoptosis of bladder transitional cell carcinoma cells
verfasst von
Haiyan Zhu
Yuxin Tang
Xiangyang Zhang
Xianzhen Jiang
Yong Wang
Yu Gan
Jianfu Yang
Publikationsdatum
01.03.2015
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 3/2015
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-015-0541-y

Weitere Artikel der Ausgabe 3/2015

Medical Oncology 3/2015 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.