Expression of the ERBB3 gene product in breast cancer

Abstract

Summary Abnormalities of the EGF receptor and/or the related ERBB2 receptor occur in a significant proportion of cases of human breast cancer and are important influences in the behaviour of this tumour type.In this report we demonstrate by nucleic acid analysis and immunohistochemistry that the recently recognised third member of this gene Costa et al., 1988). Overexpression of the ERBB2 protein is also a marker of poor prognosis for node-positive disease (Slamon et al., 1987) and probably also for node-negative disease (Perren, 1991). More exciting, however, is the accumulating evidence that the ERBB2 receptor protein has potential as a target for antibody-directed therapy (Shepard et al., 1991) and other approaches such as inhibition of receptor dimerisation and tyrosine kinase function (Gullick 1990b Thirty six biopsy samples of non-neoplastic breast tissue

c-erbB3 and c-erbB4 expression is a feature of the endocrine responsive phenotype in clinical breast cancer

“…As for the mRNA, status levels of c-erbB3 protein were found to be in agreement with those reported in the literature as positive (ZR75.1, MCF-7, MDA 453; Lemoine et al, 1992;Kraus et al, 1993) or negative (MDA 231, A431 Rajkumar and Gullick, 1994) respectively for c-erbB3 protein (not illustrated). Having thus standardized the conditions of the assay, an immunocytochemical analysis of c-erbB3 in group 2 primary breast cancer specimens revealed membrane immunostaining in 84% specimens.…”

“…The developed RT ± PCR procedure for the detection of c-erbB3 and c-erbB4 mRNA was tested further using a small sub-group of breast tumour samples and was found to be highly reproducible, with a mean densitometry variance of only *4% (not illustrated). Furthermore, analysis of c-erbB3 mRNA expression by RT ± PCR for a series of breast cancer cell lines was in concurrence with the literature, both for those reported as positive (ZR75.1, MCF-7, MDA 453; Lemoine et al, 1992;Kraus et al, 1993;Chan et al, 1995) and negative (MDA 231, A431;Rajkumar and Gullick, 1994) respectively for c-erbB3 mRNA and protein (not illustrated).…”

“…Over expression of both c-erbB3 in some breast tumours (Gasparini et al, 1994;Lemoine et al, 1992) and c-erbB4 in some cell lines (Plowman et al, 1993b) has been previously reported. However the frequency of their expression in ER positive and ER negative disease is as yet unknown, as is their e ect (if any) on clinical endocrine response.…”

“…Con®dence in the optimised RT ± PCR procedure for the detection of c-erbB3 mRNA was initially tested on a series of cell monolayers reported in the literature as positive (ZR75.1, MCF-7, MDA 453; Lemoine et al, 1992;Chan et al, 1995;Rajkumar et al, 1995) or negative (MDA 231, A431; Rajkumar and Gullick, 1994) respectively for c-erbB3 protein or mRNA. Furthermore, assay conditions were carefully optimized by performing simultaneous RT ± PCR of each speci®c primer in combination with aactin on 10 of the breast cancer samples using a range of cycle numbers (20 ± 32) and using conditions identical to those described previously (Knowlden et al, 1997).…”

“…c-erbB3 protein Immunocytochemical assay The proficiency of the optimized immunocytochemical assay using the RTJ1 antibody (Rajkumar et al, 1993) for detection of c-erbB3 was initially tested on a series of 3.7% formaldehyde-®xed cell monolayers reported in the literature as positive (ZR75.1, MCF-7, MDA 453; Lemoine et al, 1992;Rajkumar et al, 1995) or negative (MDA 231, A431 Rajkumar and Gullick, 1994) respectively for c-erbB3 protein. Further con®dence in the speci®city of the assay for c-erbB3 was derived from control sections of each clinical sample which were incubated with a dilution of RTJ1 primary antibody matched to that of the paired tests but pre-absorbed for 5 h with appropriate c-erbB3 peptide (i.e.…”