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RCI-Oncogene viruses for tumor specific knockout

DISCOVERIES (ISSN 2359-7232), 2016, April-June issue

CITATION: 

Wang W, Dong B, Ittmann MM, Yang F. A Versatile Gene Delivery System for Efficient and Tumor Specific Gene Manipulation in vivo. Discoveries 2016, April-June; 4(2): e58. DOI: 10.15190/d.2016.5

Submitted: June 10, 2016; Revised: June 21, 2016; Accepted: June 21, 2016; Published: June 22, 2016;

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A Versatile Gene Delivery System for Efficient and Tumor Specific Gene Manipulation in vivo

Wei Wang (1), Bingning Dong (1), Michael M. Ittmann (2), Feng Yang (1,*)

(1) Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA

(2) Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA

*Correspondence to: Feng Yang, Ph.D., Department of Molecular and Cellular Biology, One Baylor Plaza, Baylor College of Medicine, Houston, TX, 77030, USA; Email: fyang@bcm.edu

Abstract

The Replication-Competent Avian Sarcoma-leukosis virus long-terminal repeat with splice acceptor (RCAS)-Tumor Virus A (TVA) gene delivery system has been created based on the fact that avian sarcoma leukosis virus subgroup A only infects cells expressing its receptor, TVA. This system has been successfully applied to create various mouse models for human cancers. Here we briefly discuss the advantages and the potential caveats of using this RCAS-TVA gene delivery system in cancer research. We also introduce and discuss how our newly designed RCAS-based gene delivery system (RCI-Oncogene, for RCAS-Cre-IRES-Oncogene) allows concise and efficient manipulation of gene expression in tumors in vivo, and how this system can be used to rapidly study the biological function of gene(s) and/or the collaborative actions of multiple genes in regulating tumor initiation, progression and/or metastasis. 

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References

1.   Federspiel MJ, Swing DA, Eagleson B, Reid SW, Hughes SH. Expression of transduced genes in mice generated by infecting blastocysts with avian leukosis virus-based retroviral vectors. Proc Natl Acad Sci U S A 1996, 93(10): 4931-4936.

2. Morton JP, Mongeau ME, Klimstra DS, Morris JP, Lee YC, Kawaguchi Y, et al. Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis. Proc Natl Acad Sci U S A 2007, 104(12): 5103-5108.

3. Lewis BC, Klimstra DS, Socci ND, Xu S, Koutcher JA, Varmus HE. The absence of p53 promotes metastasis in a novel somatic mouse model for hepatocellular carcinoma. Mol Cell Biol 2005, 25(4): 1228-1237.

4. Du Z, Podsypanina K, Huang S, McGrath A, Toneff MJ, Bogoslovskaia E, et al. Introduction of oncogenes into mammary glands in vivo with an avian retroviral vector initiates and promotes carcinogenesis in mouse models. Proc Natl Acad Sci U S A 2006, 103(46): 17396-17401.

5. Montaner S, Sodhi A, Molinolo A, Bugge TH, Sawai ET, He Y, et al. Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell 2003, 3(1): 23-36.

6. Federspiel MJ, Bates P, Young JA, Varmus HE, Hughes SH. A system for tissue-specific gene targeting: transgenic mice susceptible to subgroup A avian leukosis virus-based retroviral vectors. Proc Natl Acad Sci U S A 1994, 91(23): 11241-11245.

7. Bu W, Zhang X, Dai H, Huang S, Li Y. Mammary cells with active Wnt signaling resist ErbB2-induced tumorigenesis. PLoS One 2013, 8(11): e78720.

8. Schedin P. Pregnancy-associated breast cancer and metastasis. Nature Reviews Cancer 2006, 6(4): 281-291.

9. Bu W, Chen J, Morrison GD, Huang S, Creighton CJ, Huang J, et al. Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer. Oncogene 2011, 30(43): 4399-4409.

10. Haricharan S, Hein SM, Dong J, Toneff MJ, Aina OH, Rao PH, et al. Contribution of an alveolar cell of origin to the high-grade malignant phenotype of pregnancy-associated breast cancer. Oncogene 2014, 33(50): 5729-5739.

11. Holloway KR, Sinha VC, Bu W, Toneff M, Dong J, Peng Y, et al. Targeting Oncogenes into a Defined Subset of Mammary Cells Demonstrates That the Initiating Oncogenic Mutation Defines the Resulting Tumor Phenotype. Int J Biol Sci 2016, 12(4): 381-388.

12. Haricharan S, Dong J, Hein S, Reddy JP, Du Z, Toneff M, et al. Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy. Elife 2013, 2: e00996.

13. Du Z, Li Y. RCAS-TVA in the mammary gland: an in vivo oncogene screen and a high fidelity model for breast transformation? Cell Cycle 2007, 6(7): 823-826.

14. Yang F, Zhang Y, Ressler SJ, Ittmann MM, Ayala GE, Dang TD, et al. FGFR1 Is Essential for Prostate Cancer Progression and Metastasis. Cancer Res 2013, 73(12): 3716-3724.

15. Pirvola U, Ylikoski J, Trokovic R, Hebert JM, McConnell SK, Partanen J. FGFR1 is required for the development of the auditory sensory epithelium. Neuron 2002, 35(4): 671-680.

16. Trokovic N, Trokovic R, Mai P, Partanen J. Fgfr1 regulates patterning of the pharyngeal region. Genes Dev 2003, 17(1): 141-153.

17. Trokovic R, Trokovic N, Hernesniemi S, Pirvola U, Vogt Weisenhorn DM, Rossant J, et al. FGFR1 is independently required in both developing mid- and hindbrain for sustained response to isthmic signals. Embo J 2003, 22(8): 1811-1823.

18. Jin C, McKeehan K, Wang F. Transgenic mouse with high Cre recombinase activity in all prostate lobes, seminal vesicle, and ductus deferens. Prostate 2003, 57(2): 160-164.

19. Gingrich JR, Barrios RJ, Morton RA, Boyce BF, DeMayo FJ, Finegold MJ, et al. Metastatic prostate cancer in a transgenic mouse. Cancer Res 1996, 56(18): 4096-4102.

20. Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 2001, 15(24): 3243-3248.

21. Ryan MD, Drew J. Foot-and-mouth disease virus 2A oligopeptide mediated cleavage of an artificial polyprotein. EMBO J 1994, 13(4): 928-933.

22. Kim JH, Lee SR, Li LH, Park HJ, Park JH, Lee KY, et al. High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice. PLoS One 2011, 6(4): e18556.

23. Siwko SK, Bu W, Gutierrez C, Lewis B, Jechlinger M, Schaffhausen B, et al. Lentivirus-mediated oncogene introduction into mammary cells in vivo induces tumors. Neoplasia 2008, 10(7): 653-662, 651 p following 662.

24. Cho H, Herzka T, Zheng W, Qi J, Wilkinson JE, Bradner JE, et al. RapidCaP, a novel GEM model for metastatic prostate cancer analysis and therapy, reveals myc as a driver of Pten-mutant metastasis. Cancer Discov 2014, 4(3): 318-333.

25. Cho H, Herzka T, Stahlhut C, Watrud K, Robinson BD, Trotman LC. Rapid in vivo validation of candidate drivers derived from the PTEN-mutant prostate metastasis genome. Methods 2015, 77-78: 197-204.

26. Nowak DG, Cho H, Herzka T, Watrud K, DeMarco DV, Wang VM, et al. MYC Drives Pten/Trp53-Deficient Proliferation and Metastasis due to IL6 Secretion and AKT Suppression via PHLPP2. Cancer Discov 2015, 5(6): 636-651.

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