Cytogenetic characterization and gene expression profiling of the trastuzumab-resistant breast cancer cell line JIMT-1.
Författare
Summary, in English
Resistance to the HER-2 targeting drug trastuzumab can be observed clinically, but the lack of suitable experimental models hampers studies of resistance mechanisms. We characterized a HER-2–positive carcinoma cell line (JIMT-1) derived from a 62-year-old breast cancer patient which was clinically resistant to trastuzumab. Multicolor fluorescence in situ hybridization revealed a complex hyperdiploid karyotype with numerous marker chromosomes and unbalanced translocations. Comparative genomic hybridization (CGH) revealed numerous regions of copy number aberration (CNA). Further analysis by array CGH identified 27 regions of CNA (16 amplified, 11 deleted). Thirty-eight percent of the genes in the amplified regions were overexpressed, compared to only 9% in regions of normal copy number ratios (CNR). Accordingly, 26% of the genes in the deleted regions were underexpressed, compared to 10% in regions of normal CNR. Most amplified and overexpressed genes were located on chromosome 1 as well as on 8q, 12q14.1, 17q11not, vert, similarq21, and 20q13. In 17q11not, vert, similarq21, we identified two separate amplicons, the HER-2 amplicon and a previously unreported amplicon at 17q21.31. Several aberrant genes are implicated in cancer development (e.g., JUN, CDK4, and SLUG protooncogenes, as well as the drug/hormone–metabolizing genes GSTM1 and CYP24). We conclude that cytogenetic and expression profiling of JIMT-1 revealed several new features that need further characterization and may shed light on trastuzumab resistance.
Avdelning/ar
Publiceringsår
2007
Språk
Engelska
Sidor
95-106
Publikation/Tidskrift/Serie
Cancer Genetics and Cytogenetics
Volym
172
Issue
2
Fulltext
- Available as PDF - 951 kB
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Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Cancer and Oncology
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 0165-4608