The Establishment of a Growth-controllable Orthotopic Bladder Cancer Model Through the Down-regulation of C-myc Expression

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Sep 9

PMID 28881578

Citations 6

Authors

Ho Kyung Seo

Seung-Phil Shin

Na-Rae Jung

Whi-An Kwon

Kyung-Chae Jeong

Sang-Jin Lee

Affiliations

Soon will be listed here.

Abstract

To properly evaluate the biological effects of immunotherapy, it is critical to utilize a model of cancer in immune-competent mice. Currently, MBT-2 is the most common murine bladder cancer cell line used in orthotopic bladder cancer models, even though this cell type often has an inappropriate genetic mutation landscape. In these models, after tumors are detected with imaging, the mouse usually dies within two to three weeks due to post-renal azotemia caused by the rapidly growing mass. This event prohibits the evaluation of tumor behavior upon intravesical drug treatment. We explored whether an shRNA-induced decrease in the expression of the oncogene in MBT-2 cells could slow down their proliferation and tumor growth. We transduced MBT-2 cells with shRNA lentiviruses that bound c-myc, established MBT2.cMYCshRNA and confirmed the retardation of the growth of tumors implanted in C3H/He mice. Accordingly, this study suggests that this novel orthotopic bladder cancer model in immune-competent mice may be more appropriate for the analysis of the effects of the intravesical instillation of immunotherapeutic agents.

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References

Jager W, Horiguchi Y, Shah J, Hayashi T, Awrey S, Gust K . Hiding in plain view: genetic profiling reveals decades old cross contamination of bladder cancer cell line KU7 with HeLa. J Urol. 2013; 190(4):1404-9. PMC: 3805942. DOI: 10.1016/j.juro.2013.03.009. View

Chan E, Patel A, Heston W, Larchian W . Mouse orthotopic models for bladder cancer research. BJU Int. 2009; 104(9):1286-91. DOI: 10.1111/j.1464-410X.2009.08577.x. View

Witjes J . Management of BCG failures in superficial bladder cancer: a review. Eur Urol. 2006; 49(5):790-7. DOI: 10.1016/j.eururo.2006.01.017. View

Papamichalis G, Francia K, Karachaliou F, Anastasiades O, Spandidos D . Expression of the c-myc oncoprotein in human metaplastic epithelial cells of fibrocystic disease. Anticancer Res. 1988; 8(6):1217-22. View

Dang C . MYC on the path to cancer. Cell. 2012; 149(1):22-35. PMC: 3345192. DOI: 10.1016/j.cell.2012.03.003. View

Zhang N, Li D, Shao J, Wang X . Animal models for bladder cancer: The model establishment and evaluation (Review). Oncol Lett. 2015; 9(4):1515-1519. PMC: 4356294. DOI: 10.3892/ol.2015.2888. View

Phesse T, Myant K, Cole A, Ridgway R, Pearson H, Muncan V . Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo. Cell Death Differ. 2014; 21(6):956-66. PMC: 4013513. DOI: 10.1038/cdd.2014.15. View

Cole A, Myant K, Reed K, Ridgway R, Athineos D, van den Brink G . Cyclin D2-cyclin-dependent kinase 4/6 is required for efficient proliferation and tumorigenesis following Apc loss. Cancer Res. 2010; 70(20):8149-58. PMC: 2974087. DOI: 10.1158/0008-5472.CAN-10-0315. View

Zhang Z, Pak J, Shapiro E, Sun T, Wu X . Urothelium-specific expression of an oncogene in transgenic mice induced the formation of carcinoma in situ and invasive transitional cell carcinoma. Cancer Res. 1999; 59(14):3512-7. View

10.

Jager W, Moskalev I, Janssen C, Hayashi T, Awrey S, Gust K . Ultrasound-guided intramural inoculation of orthotopic bladder cancer xenografts: a novel high-precision approach. PLoS One. 2013; 8(3):e59536. PMC: 3608695. DOI: 10.1371/journal.pone.0059536. View

11.

Bracarda S, Altavilla A, Hamzaj A, Sisani M, Marrocolo F, Del Buono S . Immunologic checkpoints blockade in renal cell, prostate, and urothelial malignancies. Semin Oncol. 2015; 42(3):495-505. DOI: 10.1053/j.seminoncol.2015.02.004. View

12.

Weldon T, Soloway M . Susceptibility of urothelium to neoplastic cellular implantation. Urology. 1975; 5(6):824-7. DOI: 10.1016/0090-4295(75)90367-2. View

13.

Nord H, Segersten U, Sandgren J, Wester K, Busch C, Menzel U . Focal amplifications are associated with high grade and recurrences in stage Ta bladder carcinoma. Int J Cancer. 2009; 126(6):1390-402. DOI: 10.1002/ijc.24954. View

14.

Shapiro A, KELLEY D, Oakley D, Catalona W, Ratliff T . Technical factors affecting the reproducibility of intravesical mouse bladder tumor implantation during therapy with Bacillus Calmette-Guérin. Cancer Res. 1984; 44(7):3051-4. View

15.

Mariani-Costantini R, Escot C, Theillet C, Gentile A, Merlo G, Lidereau R . In situ c-myc expression and genomic status of the c-myc locus in infiltrating ductal carcinomas of the breast. Cancer Res. 1988; 48(1):199-205. View

16.

Chin J, Kadhim S, Garcia B, Kim Y, Karlik S . Magnetic resonance imaging for detecting and treatment monitoring of orthotopic murine bladder tumor implants. J Urol. 1991; 145(6):1297-301. DOI: 10.1016/s0022-5347(17)38618-4. View

17.

Oyasu R . Epithelial tumours of the lower urinary tract in humans and rodents. Food Chem Toxicol. 1995; 33(9):747-55. DOI: 10.1016/0278-6915(95)00042-z. View

18.

Mickey D, MICKEY G, MURPHY W, Niell H, Soloway M . In vitro characterization of four N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced mouse bladder tumors. J Urol. 1982; 127(6):1233-7. DOI: 10.1016/s0022-5347(17)54305-0. View

19.

Lu Y, Liu P, Wen W, Grubbs C, Townsend R, Malone J . Cross-species comparison of orthologous gene expression in human bladder cancer and carcinogen-induced rodent models. Am J Transl Res. 2010; 3(1):8-27. PMC: 2981423. View

20.

Guerin M, Barrois M, Terrier M, Spielmann M, Riou G . Overexpression of either c-myc or c-erbB-2/neu proto-oncogenes in human breast carcinomas: correlation with poor prognosis. Oncogene Res. 1988; 3(1):21-31. View