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| Status |
Public on Aug 01, 2011 |
| Title |
Amplified genes are not necessarily over expressed, they can be unchanged or down regulated in cervical cancer cell lines [expression array data] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Several copy number altered regions (CNA) have been identified in the genome of cervical cancer, especially amplifications of 3q and 5p. However, the contribution of those alterations to cervical carcinogenesis is still a matter of debate, since genome-wide, there is a lack of correlation between CNAs and gene expression. In this study, we investigated whether the CNAs in cell lines (CaLo, CasKi, HeLa, SiHa), at a gene-by-gene level, are related to changes in gene expression. On average 19.2% of the whole genome of cell lines had CNA. However, only 2.4% consisted of minimal recurrent regions (MRR), common to all cell lines. Whereas 3q had just some sparse common gains (13%), 5p was entirely duplicated recurrently. Genome-wide, only 11% of genes located in CNAs changed gene expression. In contrast, the rate increased over 3 fold times in MRRs. Chr 5p was confirmed entirely amplified by FISH. In spite of this, at most 32.9% of the explored genes in 5p (n=202) were de-regulated. In 3q, the rate was just 11.8%. Even in 3q26, which had five MRRs and 38.7% of SNPs was gained recurrently, the rate rose slightly to 13.6% (10 out of 73). Interestingly, up to 16% of de-regulated genes in 5p and 80% in 3q26 were down-regulated, suggesting additional factors are involved in gene repression. The de-regulated genes in 3q and 5p were found in clusters, suggesting local chromatin factors may also influence gene expression. In regions amplified discontinuously, the rate of down-regulated genes rose steadily as the number of amplified SNPs increased (p<0.01, Spearman's correlation). This suggests partial gene amplification as a mechanism of silencing gene expression. Additional genes were identified up- or down-regulated in 5p and 3q, which could be involved in cervical carcinogenesis, especially implicated in apoptosis. Those include CLPTM1L, AHRR, PDCD6 and DAP in 5p and TNFSF10 and ECT2 in 3q. Overall, the gene expression and copy number profiles suggest other factors, like epigenetic or chromatin domains, may influence gene expression within the entirely amplified genome segments. Further studies are needed to elucidate how these mechanisms regulate gene expression.
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| Overall design |
We analyzed four cervical cancer cell lines and normal exocervix tissue from 10 healthy female subjects using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. Biological replicates were performed for the cell lines.
biological replicate: Calo-a, Calo-b, Calo-c
biological replicate: Caski-a, Caski-b, Caski-c
biological replicate: Hela-a, Hela-b, Hela-c
biological replicate: Siha-a, Siha-b, Siha-c
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| Contributor(s) |
Berumen J, Vazquez-Mena O |
| Citation missing |
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| Submission date |
May 11, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Jaime Berumen |
| E-mail(s) |
jaimeberumen@hotmail.com
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| Phone |
+52(55)27892000
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| Organization name |
Universidad Nacional Autonoma de Mexico
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| Department |
Departamento de Medicina Experimental
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| Lab |
Unidad de Medicina Genómica
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| Street address |
Dr. Balmis #148 Col. Doctores
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| City |
Mexico City |
| ZIP/Postal code |
06726 |
| Country |
Mexico |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (22)
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| GSM722570 |
Cervical cancer cell line CaLo_rep1 |
| GSM722571 |
Cervical cancer cell line CaLo_rep2 |
| GSM722572 |
Cervical cancer cell line CaSki_rep1 |
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| This SubSeries is part of SuperSeries: |
| GSE29245 |
Amplified genes are not necessarily over expressed, they can be unchanged or down regulated in cervical cancer cell lines |
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| Relations |
| BioProject |
PRJNA142961 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE29216_RAW.tar |
91.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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