It was concluded that the neu gene is a distinct novel gene, as it is not coamplified with sequences encoding the EGF receptor in the genome of the A431 tumor line and it maps to human chromosome 17.
Subversion of the EGF mitogenic signal through expression of a truncated receptor 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.
A survey of human tumor cell lines for increased PDGF or EGF receptors identified 5 lines which bind from 6 to 13 times more EGF than normal human fibroblasts.
Southern blot-hybridization analysis of DNAs from human tumors demonstrated amplification of the epidermal growth factor (EGF) receptor gene in 10 of 12 squamous cell carcinoma cell lines tested and in none of 18 tumor cell lines of nonsquamous cell carcinomas.
There was no correlation between the proliferative activity of the tumours as measured by thymidinekinase activity and the amount of EGF receptors in the tumour.
However, the transfected BCNS fibroblasts that escaped senescence were anchorage-dependent even after exposure to the tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate (TPA), epidermal growth factor (EGF) or platelet-derived growth factor (PDGF).
The products of these mutated c-erbB genes were about 30 kilodalton (kDa) smaller than the normal 170-kDa EGF receptor, and the tumor cell membrane fractions containing the 140-kDa abnormal EGF receptor showed a significant elevation of tyrosine kinase activity without its ligand.
Scatchard binding curves obtained in 21 of the 36 tumors and seven of eight of the normal lung preparations showed high and low affinity sites for EGF receptors on all but two tumor membranes.
In 7 patients, expression level and gene copy numbers of erbB-2 or EGF receptor were similarly altered in the primary tumor and metastatic lesions derived from the same patient.
In addition, using chimeric constructs of the stromelysin promoter linked to the bacterial gene chloramphenicol acetyltransferase (CAT), we show that the elements required for the tumor promoter phorbol myristate acetate (PMA), epidermal growth factor (EGF), and interleukin 1 beta (IL-1 beta) induction are contained on a 307 base pair fragment which includes approximately 270 base pairs (bp) of 5'-flanking DNA.
The 5' flanking region of the pS2 gene contains a complex enhancer region responsive to oestrogens, epidermal growth factor, a tumour promoter (TPA), the c-Ha-ras oncoprotein and the c-jun protein.
In this report the regulation of extracellular-associated plasminogen activator (PA) production by EGF in human squamous cell carcinomas and its influence on tumor cell-mediated degradation of extracellular matrix (ECM) is described.
It was also found that the mean relative level of EGF mRNA in those tumors which were ER and PgR negative [9.8 +/- 5.6 (SEM) relative units] was significantly lower than those tumors which were ER and PgR positive (40.5 +/- 6.4 relative units, P less than 0.05) or ER positive and PgR negative (68.4 +/- 19.9 relative units, P less than 0.005).
Our experiments reveal underexpression of the proEGF gene in all tumors analyzed (21 of 21) and overexpression of the genes for proTGF-alpha (33 of 33 analyzed) and EGF receptor (22 of 23 analyzed) in tumor samples, when compared with normal kidney tissue.