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J Proteome Res. 2016 Nov 4;15(11):4047-4059. Epub 2016 Aug 16.

Drug Resistance in Colorectal Cancer Cell Lines is Partially Associated with Aneuploidy Status in Light of Profiling Gene Expression.

Guo J1,2,3, Xu S3,4, Huang X3,4, Li L3,4, Zhang C1,2, Pan Q1,2, Ren Z3,4, Zhou R3,4, Ren Y3,4, Zi J3,4, Wu L1,2, Stenvang J5, BrĂ¼nner N5, Wen B3,4, Liu S1,2,3,4.

Author information

1
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, 100101, China.
2
University of Chinese Academy of Sciences, Beijing, 100049, China.
3
BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
4
China National GeneBank-Shenzhen, BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
5
Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Section for Molecular Disease Biology, University of Copenhagen , Strandboulevarden 49, DK-2100 Copenhagen, Denmark.

Abstract

A priority in solving the problem of drug resistance is to understand the molecular mechanism of how a drug induces the resistance response within cells. Because many cancer cells exhibit chromosome aneuploidy, we explored whether changes of aneuploidy status result in drug resistance. Two typical colorectal cancer cells, HCT116 and LoVo, were cultured with the chemotherapeutic drugs irinotecan (SN38) or oxaliplatin (QxPt), and the non- and drug-resistant cell lines were selected. Whole exome sequencing (WES) was employed to evaluate the aneuploidy status of these cells, and RNAseq and LC-MS/MS were implemented to examine gene expression at both mRNA and protein level. The data of gene expression was well-matched with the genomic conclusion that HCT116 was a near diploid cell, whereas LoVo was an aneuploid cell with the increased abundance of mRNA and protein for these genes located at chromosomes 5, 7, 12, and 15. By comparing the genomic, transcriptomic, and proteomic data, the LoVo cells with SN38 tolerance showed an increased genome copy in chromosome 14, and the expression levels of the genes on this chromosome were also significantly increased. Thus, we first observed that SN38 could impact the aneuploidy status in cancer cells, which was partially associated with the acquired drug resistance.

KEYWORDS:

aneuploidy; chromosome; colorectal cancer; drug resistance; genome; proteome; transcriptome

PMID:
27457664
DOI:
10.1021/acs.jproteome.6b00387
[Indexed for MEDLINE]

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