A comparative study of genome-wide SNP, CGH microarray and protein expression analysis to explore genotypic and phenotypic mechanisms of acquired antiestrogen resistance in breast cancer
Allelic imbalance is a common feature of many malignancies. We have measured allelic imbalance in genomic DNA from the breast cancer cell lines T47D, MDA-MB-231, two antiestrogen sensitive (MCF7N and MCF7L) and two resistant MCF7 cell lines (MMU2 and LCC9) using single nucleotide polymorphism (SNP) oligonucleotide microarrays. DNA from MCF7(L) and MMU2 cells was also analysed by comparative genome hybridisation (CGH) to compare with SNP microarray data. Proteins previously determined to be involved in disease progression were quantified by Western blot and compared to array data. The SNP and CGH array both detected cytogenetic abnormalities commonly found in breast cancer: amplification of chromosomes 11q13-14.1, 17q and 20q containing cyclin D1, BCAS1 and 3 (Breast Cancer Amplified Sequence) and AIB1 (Amplified in Breast cancer) genes; losses at 6q, 9p and X chromosomes, which included ERalpha (Estrogen Receptor alpha) and p16 ( INK4A ) genes. However the SNP chip array data additionally identified regions of loss of heterozygosity (LOH) followed by duplication of the remaining allele-uniparental disomy (UPD). Good concordance between SNP arrays and CGH analyses was observed, however there was poor correlation between gene copy number and protein levels between the cell lines. There were reductions in ERalpha, cyclin D1 and p27 protein levels whilst p21 protein levels were elevated in antiestrogen resistant MCF7 cell lines. Although protein levels varied there was no difference in gene copy number. This study shows SNP and CGH array analysis are powerful tools for analysis of allelic imbalance in breast cancer. However, the antiestrogen resistant phenotype was likely to be due to changes in gene expression and protein degradation rather than in altered gene copy number.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2008 |
|---|---|
| Erschienen: |
2008 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:111 |
|---|---|
| Enthalten in: |
Breast cancer research and treatment - 111(2008), 1 vom: 30. Sept., Seite 55-63 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Johnson, Neil [VerfasserIn] |
|---|
| Themen: |
Comparative Study |
|---|
| Anmerkungen: |
Date Completed 16.09.2008 Date Revised 29.01.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM174034687 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM174034687 | ||
| 003 | DE-627 | ||
| 005 | 20231223135035.0 | ||
| 007 | tu | ||
| 008 | 231223s2008 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0580.xml |
| 035 | |a (DE-627)NLM174034687 | ||
| 035 | |a (NLM)17899364 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Johnson, Neil |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A comparative study of genome-wide SNP, CGH microarray and protein expression analysis to explore genotypic and phenotypic mechanisms of acquired antiestrogen resistance in breast cancer |
| 264 | 1 | |c 2008 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 16.09.2008 | ||
| 500 | |a Date Revised 29.01.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Allelic imbalance is a common feature of many malignancies. We have measured allelic imbalance in genomic DNA from the breast cancer cell lines T47D, MDA-MB-231, two antiestrogen sensitive (MCF7N and MCF7L) and two resistant MCF7 cell lines (MMU2 and LCC9) using single nucleotide polymorphism (SNP) oligonucleotide microarrays. DNA from MCF7(L) and MMU2 cells was also analysed by comparative genome hybridisation (CGH) to compare with SNP microarray data. Proteins previously determined to be involved in disease progression were quantified by Western blot and compared to array data. The SNP and CGH array both detected cytogenetic abnormalities commonly found in breast cancer: amplification of chromosomes 11q13-14.1, 17q and 20q containing cyclin D1, BCAS1 and 3 (Breast Cancer Amplified Sequence) and AIB1 (Amplified in Breast cancer) genes; losses at 6q, 9p and X chromosomes, which included ERalpha (Estrogen Receptor alpha) and p16 ( INK4A ) genes. However the SNP chip array data additionally identified regions of loss of heterozygosity (LOH) followed by duplication of the remaining allele-uniparental disomy (UPD). Good concordance between SNP arrays and CGH analyses was observed, however there was poor correlation between gene copy number and protein levels between the cell lines. There were reductions in ERalpha, cyclin D1 and p27 protein levels whilst p21 protein levels were elevated in antiestrogen resistant MCF7 cell lines. Although protein levels varied there was no difference in gene copy number. This study shows SNP and CGH array analysis are powerful tools for analysis of allelic imbalance in breast cancer. However, the antiestrogen resistant phenotype was likely to be due to changes in gene expression and protein degradation rather than in altered gene copy number | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Estrogen Receptor Modulators |2 NLM | |
| 700 | 1 | |a Speirs, Valerie |e verfasserin |4 aut | |
| 700 | 1 | |a Curtin, Nicola J |e verfasserin |4 aut | |
| 700 | 1 | |a Hall, Andrew G |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Breast cancer research and treatment |d 1992 |g 111(2008), 1 vom: 30. Sept., Seite 55-63 |w (DE-627)NLM01302132X |x 1573-7217 |7 nnns |
| 773 | 1 | 8 | |g volume:111 |g year:2008 |g number:1 |g day:30 |g month:09 |g pages:55-63 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 111 |j 2008 |e 1 |b 30 |c 09 |h 55-63 | ||