Disease relevance of Erbb2

• FVB female mice transgenic for the rat neu proto-oncogene [mouse mammary tumor virus (MMTV)-neu] developed mammary tumors between 7 and 12 months of age, whereas FVB x C57Bl/6 (F1) MMTV-neu mice had tumor latencies greater than 18 months [1].
• Neu-induced retroviral rat mammary carcinogenesis: a novel chemoprevention model for both hormonally responsive and nonresponsive mammary carcinomas [2].
• Heregulin-stimulated signaling in rat pheochromocytoma cells. Evidence for ErbB3 interactions with Neu/ErbB2 and p85 [3].
• EtNU-induced schwannomas exclusively exhibit an A:T T:A transversion mutation of the neu/Erbb-2 gene located on chromosome 10, with subsequent loss of the wild-type neu/Erbb-2 allele at a post-initiation stage [4].
• In week 52, the incidence of gastric cancers was significantly lover in rats treated with the C-erbB-2 antisense oligonucleotide than in rats treated with the sense oligonucleotide [5].

High impact information on Erbb2

• We have purified to homogeneity a 44 kd glycoprotein from the medium of ras-transformed cells that stimulates phosphorylation of the Neu protein and retains activity after elution from the polyacrylamide gel [6].
• Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit [7].
• The neu proto-oncogene may be converted into a dominantly transforming oncogene by a single point mutation [8].
• Activity-dependent regulation of Neu differentiation factor/neuregulin expression in rat brain [9].
• This mitogen is presented to Schwann cells by axons and induces proliferation through an interaction that involves p185erbB2 on Schwann cells [10].

Chemical compound and disease context of Erbb2

• A 50-residue peptide, Neu(exp), containing the transmembrane portion of the receptor tyrosine kinase, Neu, was designed for expression in Escherichia coli [11].
• Administration of the C-erbB-2 antisense oligonucleotide also significantly decreased the bromodeoxyuridine-labeling index and significantly increased the apoptotic index of gastric cancers [5].
• In summary, OEA improved ventricular remodeling and augmented cardiac function in doxorubicin cardiomyopathy, possibly involving activation of Neu/ErbB2 and Ras-Erk signaling [12].
• CONCLUSIONS: We conclude that genistein in the diet can downregulate the EGF and ErbB2/Neu receptors in the rat prostate with no apparent adverse toxicity to the host [13].
• Ethylnitrosourea (ENU) given transplacentally to rats induces schwannomas of the cranial, spinal, and peripheral nerves, with a high frequency of mutations in the neu proto-oncogene [14].

Biological context of Erbb2

• Assignment of Erbb2 to rat chromosome band 10q32.1 by in situ hybridization [15].
• Neu differentiation factor stimulates phosphorylation and activation of the Sp1 transcription factor [16].
• The results complemented those of the deletion studies and led us to conclude that transcriptional regulation of the neu proto-oncogene involves at least one negative and three positive trans-acting factors interacting with different cis-acting elements along the neu gene promoter [17].
• These data demonstrate the power of Drosophila genetics to unmask the molecules that signal from oncogenic ErbB-2/Neu [18].
• We have tested the effects of antibodies against components of this system (HRG beta 1 and p185erbB2) in cocultures of rat sensory neurons and human (or rat) Schwann cells to elucidate the role of these proteins in axon-induced Schwann cell proliferation [10].

Anatomical context of Erbb2

• Transgenic long-term gonadectomized rats did not develop mammary cancer, but Neu overexpression stimulated the growth of their mammary glands [19].
• Our results suggest crosstalk between the Neu proto-oncogene and AR signaling pathways in the growth of both the normal and cancerous mammary epithelium [19].
• Neu differentiation factor regulates tau protein and mRNA in cultured neonatal oligodendrocytes [20].
• The immunohistochemistry method was used to observe the number of G cells, the expression of protein of EGFR (EGF receptor), C-erbB-2, p53, p16 and bcl-2 in gastric tissue [21].
• We recently reported that a 44 kd glycoprotein secreted by transformed fibroblasts stimulates tyrosine phosphorylation of the product of the neu proto-oncogene and induces differentiation of mammary tumor cells to milk-producing, growth-arrested cells [7].

Associations of Erbb2 with chemical compounds

• Androgen-dependent mammary carcinogenesis in rats transgenic for the Neu proto-oncogene [19].
• Multiple ErbB-2/Neu Phosphorylation Sites Mediate Transformation through Distinct Effector Proteins [22].
• We show that Drosophila adaptors signal from individual phosphotyrosine sites of rat Neu [18].
• ARIA acetylcholine receptor-inducing activity protein, is a member of a family of ligands that includes the Neu differentiation factor, heregulin, and glial growth factor [23].
• We have tested this possibility by constructing a consecutive series of cysteine substitutions in the Neu juxtamembrane domain in order to force dimerization along a series of interreceptor faces [24].

Other interactions of Erbb2

• ErbB3 is an epidermal growth factor receptor-related type I tyrosine kinase receptor capable, in conjunction with ErbB2 or epidermal growth factor receptor, of transmitting proliferative and differentiative signals in a variety of cell types [25].

Analytical, diagnostic and therapeutic context of Erbb2

• Western blots of Neu 5-reactive material also show developmental and spatial correlations of apparent molecular-weight distributions expected of N-CAM-like components as well [26].
• Three-dimensional confocal analyses of BrdU and the neuronal-specific marker Neu N by double immunofluorescence confirmed their colocalization within the same cells at 72 hours and 30 days after stroke induction [27].

References