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Article

Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer

  • Authors:
    • Nayoung Kim
    • Mee Song
    • Somin Kim
    • Yujeong Seo
    • Yonghwan Kim
    • Sukjoon Yoon
  • View Affiliations / Copyright

    Affiliations: Center for Advanced Bioinformatics and Systems Medicine, Sookmyung Women's University, Seoul, Republic of Korea, Department of Life Systems, Sookmyung Women's University, Seoul, Republic of Korea
  • Pages: 367-375
    |
    Published online on: November 20, 2015
       https://doi.org/10.3892/ijo.2015.3262
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Abstract

Genetic alterations in lung cancer are distinctly represented in non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Mutation of the RB1 and CDKN2A genes, which are tightly associated with cell cycle regulation, is exclusive to SCLC and NSCLC cells, respectively. Through the systematic analysis of transcriptome and proteome datasets for 318 cancer cell lines, we characterized differential gene expression and protein regulation in RB1-mutant SCLC and CDKN2A-mutant NSCLC. Many of the genes and proteins associated with RB1-mutant SCLC cell lines belong to functional categories of gene expression and transcription, whereas those associated with CDKN2A-mutant NSCLC cell lines were enriched in gene sets of the extracellular matrix and focal adhesion. These results indicate that the loss of RB1 and CDKN2A function induces distinctively different signaling cascades in SCLC and NSCLC cells. In addition, knockdown of the RB1 gene in CKDN2A-mutant cell lines (and vice versa) synergistically inhibits cancer cell proliferation. The present study on the exclusive role of RB1 and CDKN2A mutations in lung cancer subtypes demonstrates a synthetic lethal strategy for cancer regulation.
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1 

Kim N, He N, Kim C, Zhang F, Lu Y, Yu Q, Stemke-Hale K, Greshock J, Wooster R, Yoon S, et al: Systematic analysis of genotype-specific drug responses in cancer. Int J Cancer. 131:2456–2464. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Settleman J: Cell culture modeling of genotype-directed sensitivity to selective kinase inhibitors: Targeting the anaplastic lymphoma kinase (ALK). Semin Oncol. 36(Suppl 1): S36–S41. 2009. View Article : Google Scholar : PubMed/NCBI

3 

He N, Kim N, Song M, Park C, Kim S, Park EY, Yim HY, Kim K, Park JH, Kim KI, et al: Integrated analysis of transcriptomes of cancer cell lines and patient samples reveals STK11/LKB1-driven regulation of cAMP phosphodiesterase-4D. Mol Cancer Ther. 13:2463–2473. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Knudsen ES and Knudsen KE: Tailoring to RB: Tumour suppressor status and therapeutic response. Nat Rev Cancer. 8:714–724. 2008. View Article : Google Scholar

5 

Xie Z and Liu D: Pathogenesis of molecular signaling pathways changes in smoking-induced lung cancer. Zhongguo Fei Ai Za Zhi. 12:1202–1205. 2009.in Chinese.

6 

Serrano M, Hannon GJ and Beach D: A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 366:704–707. 1993. View Article : Google Scholar : PubMed/NCBI

7 

Hernando E, Nahlé Z, Juan G, Diaz-Rodriguez E, Alaminos M, Hemann M, Michel L, Mittal V, Gerald W, Benezra R, et al: Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control. Nature. 430:797–802. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Dyson N: The regulation of E2F by pRB-family proteins. Genes Dev. 12:2245–2262. 1998. View Article : Google Scholar : PubMed/NCBI

9 

Classon M and Harlow E: The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer. 2:910–917. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T and Mitsudomi T: Mutations of the epidermal growth factor receptor gene in lung cancer: Biological and clinical implications. Cancer Res. 64:8919–8923. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II, Fong KM, Lee H, Toyooka S, Shimizu N, et al: Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 97:339–346. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Singh B, Reddy PG, Goberdhan A, Walsh C, Dao S, Ngai I, Chou TC, O-Charoenrat P, Levine AJ, Rao PH, et al: p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas. Genes Dev. 16:984–993. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Blanco R, Iwakawa R, Tang M, Kohno T, Angulo B, Pio R, Montuenga LM, Minna JD, Yokota J and Sanchez-Cespedes M: A gene-alteration profile of human lung cancer cell lines. Hum Mutat. 30:1199–1206. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Etemadmoghadam D, Weir BA, Au-Yeung G, Alsop K, Mitchell G, George J, Davis S, D'Andrea AD, Simpson K, Hahn WC, et al; Australian Ovarian Cancer Study Group. Synthetic lethality between CCNE1 amplification and loss of BRCA1. Proc Natl Acad Sci USA. 110:19489–19494. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Shoemaker RH, Monks A, Alley MC, Scudiero DA, Fine DL, McLemore TL, Abbott BJ, Paull KD, Mayo JG and Boyd MR: Development of human tumor cell line panels for use in disease-oriented drug screening. Prog Clin Biol Res. 276:265–286. 1988.PubMed/NCBI

16 

Greshock J, Bachman KE, Degenhardt YY, Jing J, Wen YH, Eastman S, McNeil E, Moy C, Wegrzyn R, Auger K, et al: Molecular target class is predictive of in vitro response profile. Cancer Res. 70:3677–3686. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Forbes SA, Bindal N, Bamford S, Cole C, Kok CY, Beare D, Jia M, Shepherd R, Leung K, Menzies A, et al: COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 39(Database): D945–D950. 2011. View Article : Google Scholar :

18 

Kim N, He N and Yoon S: Cell line modeling for systems medicine in cancers (Review). Int J Oncol. 44:371–376. 2014.

19 

Jeong E, He N, Park H, Song M, Kim N, Lee S and Yoon S: MACE: mutation-oriented profiling of chemical response and gene expression in cancers. Bioinformatics. 31:1508–1514. 2015. View Article : Google Scholar

20 

McDermott U, Sharma SV, Dowell L, Greninger P, Montagut C, Lamb J, Archibald H, Raudales R, Tam A, Lee D, et al: Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. Proc Natl Acad Sci USA. 104:19936–19941. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Vasudevan KM, Barbie DA, Davies MA, Rabinovsky R, McNear CJ, Kim JJ, Hennessy BT, Tseng H, Pochanard P, Kim SY, et al: AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer. Cancer Cell. 16:21–32. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Craft CS, Zou W, Watkins M, Grimston S, Brodt MD, Broekelmann TJ, Weinbaum JS, Teitelbaum SL, Pierce RA, Civitelli R, et al: Microfibril-associated glycoprotein-1, an extra-cellular matrix regulator of bone remodeling. J Biol Chem. 285:23858–23867. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A, et al: An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 68:6084–6091. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Tibes R, Qiu Y, Lu Y, Hennessy B, Andreeff M, Mills GB and Kornblau SM: Reverse phase protein array: validation of a novel proteomic technology and utility for analysis of primary leukemia specimens and hematopoietic stem cells. Mol Cancer Ther. 5:2512–2521. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Agresti A; John Wiley & Sons. Categorical Data Analysis. Wiley Series in Probability and Statistics. Wiley-Interscience; New York: 2002

26 

Kim N, Park H, He N, Lee HY and Yoon S: QCanvas: An Advanced Tool for Data Clustering and Visualization of Genomics Data. Genomics Inform. 10:263–265. 2012. View Article : Google Scholar

27 

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Rocco JW and Sidransky D: p16(MTS-1/CDKN2/INK4a) in cancer progression. Exp Cell Res. 264:42–55. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Gilkes DM, Semenza GL and Wirtz D: Hypoxia and the extra-cellular matrix: drivers of tumour metastasis. Nat Rev Cancer. 14:430–439. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Mazieres J, He B, You L, Xu Z and Jablons DM: Wnt signaling in lung cancer. Cancer Lett. 222:1–10. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Chang F, Steelman LS, Lee JT, Shelton JG, Navolanic PM, Blalock WL, Franklin RA and McCubrey JA: Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia. 17:1263–1293. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Wang S and Basson MD: Akt directly regulates focal adhesion kinase through association and serine phosphorylation: Implication for pressure-induced colon cancer metastasis. Am J Physiol Cell Physiol. 300:C657–C670. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Song MS, Salmena L and Pandolfi PP: The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 13:283–296. 2012.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Kim N, Song M, Kim S, Seo Y, Kim Y and Yoon S: Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer. Int J Oncol 48: 367-375, 2016.
APA
Kim, N., Song, M., Kim, S., Seo, Y., Kim, Y., & Yoon, S. (2016). Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer. International Journal of Oncology, 48, 367-375. https://doi.org/10.3892/ijo.2015.3262
MLA
Kim, N., Song, M., Kim, S., Seo, Y., Kim, Y., Yoon, S."Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer". International Journal of Oncology 48.1 (2016): 367-375.
Chicago
Kim, N., Song, M., Kim, S., Seo, Y., Kim, Y., Yoon, S."Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer". International Journal of Oncology 48, no. 1 (2016): 367-375. https://doi.org/10.3892/ijo.2015.3262
Copy and paste a formatted citation
x
Spandidos Publications style
Kim N, Song M, Kim S, Seo Y, Kim Y and Yoon S: Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer. Int J Oncol 48: 367-375, 2016.
APA
Kim, N., Song, M., Kim, S., Seo, Y., Kim, Y., & Yoon, S. (2016). Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer. International Journal of Oncology, 48, 367-375. https://doi.org/10.3892/ijo.2015.3262
MLA
Kim, N., Song, M., Kim, S., Seo, Y., Kim, Y., Yoon, S."Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer". International Journal of Oncology 48.1 (2016): 367-375.
Chicago
Kim, N., Song, M., Kim, S., Seo, Y., Kim, Y., Yoon, S."Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer". International Journal of Oncology 48, no. 1 (2016): 367-375. https://doi.org/10.3892/ijo.2015.3262
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