Polysomy of chromosome 7 is associated with amplification and overexpression of the EGF-receptor gene in a human carcinoma cell line derived from a brain metastasis.
Overexpression of the EGF-receptor gene is associated with the malignant nature of some tumors. We have recently reported the establishment of a human carcinoma cell line (T-CAR1), derived from a brain metastasis, that had 7 million EGF receptors per cell and was growth inhibited by EGF. The present study was carried out in order to further characterize the EGF-receptor protein in T-CAR1 cells, and to see if the overexpression of the EGF-receptor gene in these cells was associated with abnormalities at the genomic level. We have compared the T-CAR1 cells with the human glioblastoma cell line T-MG1, which has 135,000 EGF-receptors and is growth stimulated by EGF. The MW of the EGF receptors in T-CAR1 cells and T-MG1 cells was estimated to be 170 kDa, equal to the normal EGF-receptor. However, in T-CAR1 cells an additional protein reacted with the monoclonal antibody directed against the internal domain of the EGF receptor. The levels of EGF receptor-related RNAs in T-CAR1 cells and T-MG1 cells reflected the number of EGF receptors in these cell lines. The EGF-receptor gene was amplified ten-fold in T-CAR1 cells, while it was not amplified in T-MG1 cells. No restriction fragment length polymorphism of DNA digested with various restriction enzymes was seen in either of the cell lines. Chromosomal analysis of T-CAR1 cells showed polysomy of chromosome 7 and marker chromosomes derived partly from chromosome 7. Thus, in the T-CAR1 cell line it was an association between polysomy of chromosome 7 and EGF-receptor gene amplification.
Helseth
E
E
Institute of Cancer Research, University Hospital of Trondheim, Norway.
Brøgger
A
A
Dalen
A
A
Fure
H
H
Johansen
S G
SG
Lier
M E
ME
Skandsen
T
T
Unsgaard
G
G
Vik
R
R
D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000235:genetics* / Q000556:secondary; D002897:Chromosomes, Human, Pair 7 / Q000737:chemistry*; D004247:DNA / Q000032:analysis; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D005729:Ganglioneuroma / Q000235:genetics* / Q000556:secondary; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D007621:Karyotyping; D008970:Molecular Weight; D012313:RNA / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D012313:RNA; D004247:DNA; D066246:ErbB Receptors