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Simultaneous amplification of epidermal growth factor-receptor and multidrug-resistance genes in a newly. Established
1Department of Molecular Pathology, Universal of Texas M.D. Anderson Cancer Center, Houston, Texas 77030.
Abstract:
We have investigated amplification and expression of the epidermal growth factor (EGF)-receptor gene and the multidrug-resistance (MDRI) gene in a newly established lung adenocarcinoma cell line and its subcell lines. Of these cell lines, the EGF-receptor was amplified (64-fold) and rearranged (6.5 and 5.4 Kb with EcoRI restriction) in an early passage cell line, DMS-4CS. MDRI gene amplification (10.5-fold), accompanied by rearrangement (4.6 and 3.7 Kb with Hind III restriction), was found in the same cell line. All other subcell lines derived from DMS-4C5 failed to demonstrate any amplification of these genes. Moreover, mRNA expression of these two genes was not overproduced. Our findings seem to indicate that highly selected cells at an early stage have undergone spontaneous amplification of these genes. However, cells containing such amplified DNA sequences may exhibit growth disadvantage, and, therefore, the amplified DNA sequences were not present in the sublines. The cytogenetic study demonstrated that early passage cells, DMS-4C6, only showed one unique marker chromosome, M10, which may represent amplification of these genes in question.
Insights
Early lung adenocarcinoma cells showed spontaneous amplification of epidermal growth factor (EGF)-receptor and multidrug-resistance (MDRI) genes. However, these amplified genes were lost in later cell lines, suggesting a growth disadvantage.
Area of Science:
- Molecular Biology
- Cancer Genetics
Background:
- Lung adenocarcinoma is a significant cause of cancer mortality.
- Gene amplification and rearrangement are key mechanisms in cancer development.
Purpose of the Study:
- To investigate the amplification and expression of epidermal growth factor (EGF)-receptor and multidrug-resistance (MDRI) genes in a novel lung adenocarcinoma cell line.
- To analyze the stability of these amplified genes in derived subcell lines.
Main Methods:
- Establishment and characterization of a lung adenocarcinoma cell line (DMS-4CS) and its sublines.
- Analysis of gene amplification and rearrangement using restriction enzyme digestion.
- Assessment of gene expression via mRNA analysis.
- Cytogenetic studies to identify chromosomal abnormalities.
Main Results:
- The early passage cell line DMS-4CS exhibited significant amplification (64-fold for EGF-receptor, 10.5-fold for MDRI) and rearrangement of both genes.
- Derived subcell lines did not show amplification of these genes.
- Overproduction of mRNA for EGF-receptor and MDRI was not observed.
- Cytogenetic analysis revealed a unique marker chromosome (M10) in early passage cells, potentially linked to gene amplification.
Conclusions:
- Spontaneous gene amplification of EGF-receptor and MDRI can occur in highly selected early-stage lung adenocarcinoma cells.
- Amplified DNA sequences may confer a growth disadvantage, leading to their loss in subsequent cell generations.
- The marker chromosome M10 may be associated with the observed gene amplification events.
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