Our data indicate that one of the molecular mechanisms for overexpression of epidermal growth factor receptor in human breast cancer is epidermal growth factor receptor gene amplification without rearrangement in a subset of tumors.
Incubation of T-47D human breast cancer cells with the synthetic progestin, medroxyprogesterone acetate (MPA), resulted in a time and dose-dependent increase in epidermal growth factor-receptor (EGF-R) mRNA.
To determine whether an increase in EGFR expression might alter the estrogen responsiveness of an ER-positive human breast cancer cell line, ZR 75-1 cells were cotransfected with a plasmid containing the full-length cDNA for the human EGFR under the transcriptional control of the Harvey murine sarcoma virus (HaMSV) long terminal repeat (LTR) and with a pSV2neo plasmid.
TGFa mRNA was detected in a similar proportion of cancers as in neoplastic breast tissues but the TGFa receptor EGFR mRNA was detected in only 55% of breast cancers but in all non-neoplastic breast tissue tested.
We have investigated the DNA content and c-erbB-1 protein expression in tumor cell lines and in breast cancer patient specimens by multiparameter flow cytometry.
Levels of TGF alpha and beta and EGFR mRNA were analysed in relationship to the relapse-free and overall survival of patients with breast cancer, but none was found to predict significantly the outcome in these patients.
Both neu and epidermal growth factor receptor (EGFR) appear to have a close correlation between overexpression of the gene product and outcome of disease in breast cancer; valuable information for prognosis of the disease.
The results of this study suggest that c-erbB-2 protein overexpression, a marker of poor prognosis in breast cancer, is associated with a lack of response to endocrine therapy on relapse, and particularly in combination with EGFR may be useful in directing therapeutic choices.
Amplification of HER-2/neu, a protooncogene related to the epidermal growth factor receptor, has prognostic significance in patients with breast cancer.
Fine mapping by native genomic blotting revealed the presence of multiple protein footprints in both the promoter and first intron of the EGFR gene in MDA-MB-468 cells, a breast cancer cell line that overexpresses the EGFR gene.
We have examined the prognostic significance of TGF alpha, TGF-beta 1 and EGFR mRNA expression in a series of patients with primary breast cancer with a median follow up period of 60 months.
A receptor blotting technique was used to detect SH2 domain containing epidermal growth factor receptor (EGFR) substrates that exhibited differential expression either between normal breast epithelial cells and breast cancer cells or between different human breast cancer cell lines.
Thus, loss of bcl-2 expression in breast cancer is associated with a range of molecular markers of poor prognosis and may define part of an ER-negative, EGFR-positive phenotype.
Based on these findings, a multi-step model is proposed for the progression of breast cancer from a hormone-dependent, ER+/EGFR-phenotype to an aggressive, hormone-independent, ER-/EGFR+ stage.