TY - JOUR
T1 - Drug resistance in colorectal cancer cell lines is partially associated with aneuploidy status in light of profiling gene expression
AU - Guo, Jiao
AU - Xu, Shaohang
AU - Huang, Xuanlin
AU - Li, Lin
AU - Zhang, Congmin
AU - Pan, Qingfei
AU - Ren, Zhen
AU - Zhou, Ruo
AU - Ren, Yan
AU - Zi, Jin
AU - Wu, Lin
AU - Stenvang, Jan
AU - Brünner, Nils
AU - Wen, Bo
AU - Liu, Siqi
PY - 2016/11/4
Y1 - 2016/11/4
N2 - 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.
AB - 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.
U2 - 10.1021/acs.jproteome.6b00387
DO - 10.1021/acs.jproteome.6b00387
M3 - Journal article
C2 - 27457664
SN - 1535-3893
VL - 15
SP - 4047
EP - 4059
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 11
ER -
