Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin

Epidermal growth factor (EGF), through interaction with specific cell surface receptors, generates a pleiotropic response that, by a poorly defined mechanism, can induce proliferation of target cells1–4. Subversion of the EGF mitogenic signal through expression of a truncated receptor5–7 may be involved in transformation by the avian erythroblastosis virus (AEV) oncogene v-erb-B, suggesting that similar EGF receptor defects may be found in human neoplasias. Overexpression of EGF receptors has been reported on the epidermoid carcinoma cell line A431 (ref. 8), in various primary brain tumours9 and in squamous carcinomas10. In A431 cells the receptor gene is amplified6,11,12. Here we show that 4 of 10 primary brain tumours of glial origin which express levels of EGF receptors that are higher than normal also have amplified EGF receptor genes. Amplified receptor genes were not detected in the other brain tumours examined. Further analysis of EGF receptor defects may show that such altered expression and amplification is a particular feature of certain human tumours.

[1]  M. Groudine,et al.  Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line , 1982, Nature.

[2]  Y. Heilbronn,et al.  Extensive resection of primary malignant tumors of the left cerebral hemisphere. , 1973, Surgical neurology.

[3]  R. Schimke Gene amplification in cultured animal cells , 1984, Cell.

[4]  J. Pontén,et al.  Banding patterns in human glioma cell lines. , 2009, Hereditas.

[5]  S. Cohen,et al.  Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. , 1962, The Journal of biological chemistry.

[6]  D. Helfman,et al.  Identification of clones that encode chicken tropomyosin by direct immunological screening of a cDNA expression library. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[7]  T. Libermann,et al.  Regulation of cell proliferation by epidermal growth factor. , 1983, CRC critical reviews in biochemistry.

[8]  D. Wraith Membranes in Growth and Development , 1984 .

[9]  W. Gilbert,et al.  Sequencing end-labeled DNA with base-specific chemical cleavages. , 1980, Methods in enzymology.

[10]  Y. Shimizu,et al.  Genetics of cell surface receptors for bioactive polypeptides: binding of epidermal growth factor is associated with the presence of human chromosome 7 in human-mouse cell hybrids. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[11]  B. Roe,et al.  Human epidermal growth factor receptor cDNA is homologous to a variety of RNAs overproduced in A431 carcinoma cells , 1984, Nature.

[12]  R. Evans,et al.  Expression cloning of human EGF receptor complementary DNA: gene amplification and three related messenger RNA products in A431 cells. , 1984, Science.

[13]  F. Alt,et al.  Transposition and amplification of oncogene-related sequences in human neuroblastomas , 1983, Cell.

[14]  W. Shapiro,et al.  Isolation, karyotype, and clonal growth of heterogeneous subpopulations of human malignant gliomas. , 1981, Cancer research.

[15]  R. Kucherlapati,et al.  Genetic analysis of epidermal growth factor action: assignment of human epidermal growth factor receptor gene to chromosome 7. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Waterfield,et al.  Biosynthesis of the epidermal growth factor receptor in A431 cells. , 1984, The EMBO journal.

[17]  P. Seeburg,et al.  Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells , 1984, Nature.

[18]  G. Todaro,et al.  Nerve growth factor receptors on human melanoma cells in culture. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[19]  R. Gallo,et al.  onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient , 1982, Nature.

[20]  T. Ooi,et al.  The erbB gene of avian erythroblastosis virus is a member of the src gene family , 1983, Cell.

[21]  J. Trent,et al.  Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour , 1983, Nature.

[22]  S. Cohen,et al.  Epidermal growth factor , 1972, The Journal of investigative dermatology.

[23]  J. Taylor,et al.  Efficeint transcription of RNA into DNA by avian sarcoma virus polymerase. , 1976, Biochimica et biophysica acta.

[24]  T. Libermann,et al.  Expression of epidermal growth factor receptors in human brain tumors. , 1984, Cancer research.

[25]  M Schwab,et al.  Enhanced expression of the human gene N-myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[26]  A. Ullrich,et al.  Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences , 1984, Nature.

[27]  J. Spiess,et al.  Production of an epidermal growth factor receptor-related protein. , 1984, Science.

[28]  Y H Xu,et al.  Amplification and enhanced expression of the epidermal growth factor receptor gene in A431 human carcinoma cells. , 1984, Science.