PMID- 8579117 OWN - NLM STAT- MEDLINE DCOM- 19960311 LR - 20211203 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 148 IP - 2 DP - 1996 Feb TI - Type 1 receptor tyrosine kinases are differentially phosphorylated in mammary carcinoma and differentially associated with steroid receptors. PG - 549-58 AB - The neu/erbB-2/HER-2 proto-oncogene is amplified and/or overexpressed in up to 30% of mammary carcinomas and has been variably correlated with poor prognosis. The signaling activity of the encoded receptor tyrosine kinase is regulated by interactions with other type 1 receptors and their ligands. We have used a novel approach, phosphorylation-sensitive anti-Neu antibodies, to quantify signaling by Neu and epidermal growth factor receptor in a panel of frozen sections of mammary carcinoma specimens. We also determined the relationship of Neu, phosphorylated Neu (and epidermal growth factor receptor), and phosphotyrosine to the expression of Neu-related receptors (epidermal growth factor receptor, HER-3, and HER-4) and to prognostic factors (estrogen and progesterone receptor). We found that tyrosine phosphorylation of Neu (and hence signaling activity) is highly variable among mammary carcinomas. Neu and HER-4 were associated with divergent correlates, suggesting that they have profoundly different biological activities. These results have implications for etiology of mammary carcinoma for clinical evaluation of mammary carcinoma patients, and for development of Neu-targeted therapeutic strategies. FAU - Bacus, S S AU - Bacus SS AD - Advanced Cellular Diagnostics, Inc., Elmhurst, Illinois, USA. FAU - Chin, D AU - Chin D FAU - Yarden, Y AU - Yarden Y FAU - Zelnick, C R AU - Zelnick CR FAU - Stern, D F AU - Stern DF LA - eng GR - 5-P20-CA58202/CA/NCI NIH HHS/United States GR - CA45708/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Biomarkers, Tumor) RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) RN - 0 (Receptors, Steroid) RN - 21820-51-9 (Phosphotyrosine) RN - EC 2.7.10.1 (ERBB4 protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - EC 2.7.10.1 (Receptor, ErbB-4) SB - IM MH - Biomarkers, Tumor MH - Breast Neoplasms/*metabolism/pathology MH - ErbB Receptors/*metabolism MH - Female MH - Frozen Sections MH - Genes, erbB-2 MH - Humans MH - Immunohistochemistry MH - Phosphorylation MH - Phosphotyrosine/metabolism MH - Prognosis MH - Proto-Oncogene Mas MH - Receptor Protein-Tyrosine Kinases/*metabolism MH - Receptor, ErbB-2/*metabolism MH - Receptor, ErbB-4 MH - Receptors, Estrogen/metabolism MH - Receptors, Progesterone/metabolism MH - Receptors, Steroid/*metabolism MH - Retrospective Studies PMC - PMC1861670 EDAT- 1996/02/01 00:00 MHDA- 1996/02/01 00:01 PMCR- 1996/08/01 CRDT- 1996/02/01 00:00 PHST- 1996/02/01 00:00 [pubmed] PHST- 1996/02/01 00:01 [medline] PHST- 1996/02/01 00:00 [entrez] PHST- 1996/08/01 00:00 [pmc-release] PST - ppublish SO - Am J Pathol. 1996 Feb;148(2):549-58.