Amplified Genes May Be Overexpressed, Unchanged, or Downregulated in Cervical Cancer Cell Lines

Abstract

Several copy number-altered regions (CNAs) have been identified in the genome of cervical cancer, notably, amplifications of 3q and 5p. However, the contribution of copy-number alterations to cervical carcinogenesis is unresolved because genome-wide there exists a lack of correlation between copy-number alterations and gene expression. In this study, we investigated whether CNAs in the cell lines CaLo, CaSki, HeLa, and SiHa were associated with changes in gene expression. On average, 19.2% of the cell-line genomes had CNAs. However, only 2.4% comprised minimal recurrent regions (MRRs) common to all the cell lines. Whereas 3q had limited common gains (13%), 5p was entirely duplicated recurrently. Genome-wide, only 15.6% of genes located in CNAs changed gene expression; in contrast, the rate in MRRs was up to 3 times this. Chr 5p was confirmed entirely amplified by FISH; however, maximum 33.5% of the explored genes in 5p were deregulated. In 3q, this rate was 13.4%. Even in 3q26, which had 5 MRRs and 38.7% recurrently gained SNPs, the rate was only 15.1%. Interestingly, up to 19% of deregulated genes in 5p and 73% in 3q26 were downregulated, suggesting additional factors were involved in gene repression. The deregulated genes in 3q and 5p occurred in clusters, suggesting local chromatin factors may also influence gene expression. In regions amplified discontinuously, downregulated genes increased steadily as the number of amplified SNPs increased (p<0.01, Spearman's correlation). Therefore, partial gene amplification may function in silencing gene expression. Additional genes in 1q, 3q and 5p could be involved in cervical carcinogenesis, specifically in apoptosis. These include PARP1 in 1q, TNFSF10 and ECT2 in 3q and CLPTM1L, AHRR, PDCD6, and DAP in 5p. Overall, gene expression and copy-number profiles reveal factors other than gene dosage, like epigenetic or chromatin domains, may influence gene expression within the entirely amplified genome segments.

Small interfering RNA-induced inhibition of epithelial cell transforming sequence 2 suppresses the proliferation, migration and invasion of osteosarcoma cells

“…It has been reported that the copy number of ECT2-located 3q26 frequently increases in several cancers including head and neck, lung and cervical cancer, suggesting that a genomic imbalance may contribute to the upregulation of ECT2 in OS (10,11). ECT2 has been considered to play an oncogenic role in several malignant tumors, including ovarian cancer, retinoblastoma, pancreatic ductal adenocarcinoma, cervical and colorectal cancers, oral squamous cell carcinoma, as well as OS (9,(12)(13)(14)(15)(16)(17). In the present study, it was shown that the expression of ECT2 was significantly upregulated in OS tissues when compared with that in normal adjacent tissues.…”

“…The role of ECT2 upregulation in other cancers has been widely demonstrated (9,(12)(13)(14)(15)(16)(17); however, these studies mainly focused on its effect on cell cycle progression. For instance, Iyoda et al observed that ECT2 was notably upregulated in oral squamous cell carcinoma, and that the inhibition of ECT2 caused cell cycle arrest at the G1 phase, accompanied by the upregulation of the cyclin-dependent kinase (CDK) interacting protein/kinase inhibitory protein family of CDK inhibitors, as well as downregulation of cyclin D1, cyclin E and CDK4 (17).…”

CRR9/CLPTM1L Regulates Cell Survival Signaling and Is Required for Ras Transformation and Lung Tumorigenesis

“…A CLPTM1L haplotype has been found to confer glioma risk (16). Chromosome 5p is commonly duplicated in cervical cancer cell lines, however, of the genes within the cancer associated 5p15.33 region, only CLPTM1L is overexpressed (19). Our previous studies demonstrated that CLPTM1L is overexpressed in lung adenocarcinoma (2).…”

Correlation of CLPTM1L polymorphisms with lung cancer susceptibility and response to cisplatin-based chemotherapy in a Chinese Han population

“…Recent studies revealed that CLPTM1L expression was markedly increased in several types of tumor cell lines, including lung, cervical, and renal carcinoma lines [16,30,31]. CLPTM1L is also overexpressed in a number of different tumor tissues, such as lung cancer and laryngeal squamous cell carcinoma [15,32].…”