Simultaneous amplification of epidermal growth factor-receptor and multidrug-resistance genes in a newly. Established human lung cancer cell line.

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.