Neu differentiation factor (NDF)-induced signaling involves the activation of members of the ErbB family of receptor tyrosine kinases. Although ectopic expression of recombinant ErbB receptors has yielded valuable insight into their signaling properties, the biological function and in vivo interplay of these receptors are still poorly understood. We addressed this issue by studying NDF signalin...

BACKGROUND Betacellulin (BTC), a member of the epidermal growth factor family, is known to play an important role in regulating growth and differentiation of pancreatic beta cells. Growth-promoting actions of BTC are mediated by epidermal growth factor receptors (ErbBs), namely ErbB-1, ErbB-2, ErbB-3 and ErbB-4; however, the exact mechanism for beta cell proliferation has not been elucidated. T...

Using a polyclonal antibody that is monospecific for the erbB-2 oncogene product, an immunohistochemical study of the expression of erbB-2 protein was performed in formalin-fixed paraffin-embedded tissue sections from 260 primary gastric cancers. erbB-2 protein expression in which the reaction was localized to the cell membranes was observed in 31 (11.9%) cancers. All nontumor cells and normal ...

ErbB-2/HER2 is an oncogenic tyrosine kinase that regulates a signalling network by forming ligand-induced heterodimers with several growth factor receptors of the ErbB family. Hsp90 and co-chaperones regulate degradation of ErbB-2 but not other ErbB members. Here, we report that the role of Hsp90 in modulating the ErbB network extends beyond regulation of protein stability. The capacity of ErbB...

c-erbB-2 protein expression was investigated immunohistochemically in frozen thyroid tissue specimens from 42 patients using a polyclonal sheep antibody. c-erbB-2 immunoreactivity was detected in 12 out of 17 papillary carcinomas, while no c-erbB-2 protein immunostaining was seen in cases of follicular adenoma (five cases), follicular carcinoma (five cases) or medullary carcinoma (one case), no...

Interactions between cancer cells and their microenvironment are critical for the development and progression of solid tumors. This study is the first to examine the role of all members of the ErbB tyrosine kinase receptors (epidermal growth factor receptor [EGFR], ErbB-2, ErbB-3, or ErbB-4), expressed singly or as paired receptor combinations, in the regulation of angiogenesis both in vitro an...

The goal of this study was to investigate the relationship among immunohistochemical expression of epithelial growth factor receptor (EGFR) family proteins, p21, p27 and prognosis in patients with high-grade astrocytoma. Expression of EGFR family proteins (c-erbB-1, c-erbB-2, c-erbB-3, c-erbB-4), p21 and p27 and Ki-67 labeling index (LI) were studied in 59 samples of high-grade astrocytoma. Exp...

PSA is a 33-KDa serine protease that is produced predominantly by prostate epithelium. However, it has been shown that about 30-40% of female breast tumors produce PSA and its production is associated with the presence of estrogen and progesterone receptors. We have now developed a new tissue culture system to study PSA production in breast cancer and its association with prognostic factors...

Growth factor receptors provide unique opportunities for development of targeted anticancer therapy. Members of the type I receptor tyrosine kinase family, including epidermal growth factor (EGF) receptor (EGFR) and ErbB-2/neu, are often overexpressed in various human cancer cells, including breast. Recently, it has been shown that both ErbB-3 and ErbB-4 are receptors for heregulin (HRG)/Neu di...

Signal transduction mediated by ErbB/HER receptor tyrosine kinases is crucial for the development and maintenance of epithelial tissues, and aberrant signaling is frequently associated with malignancies of epithelial origin. This review focuses on the roles played by the Hsp90 chaperone machinery in the regulation of signaling through the ErbB/HER network, and discusses potential therapeutic st...