From a human genomic library, we obtained six v-erbB-related DNA clones. A DNA probe prepared from one of the clones, lambda 107, hybridized to EcoRI fragments of 6.4 and 13 kilobase pairs of human DNA. Neither of these fragments was amplified in A431 vulva carcinoma cells, in which the gene encoding the epidermal growth factor receptor is amplified. In addition, the probe from lambda 107 hybri...

To verity the role of metastasis-related nm23 genes in carcinogenesis and progression of ovarian carcinoma, we analyzed the mRNA levels of the nm23 genes of both isoforms, -H1 and -H2, together with those of the epidermal growth factor receptor, the c-erbB-2, and the c-erbB-3 genes in 45 ovarian carcinomas and 5 benign cystadenomas. Expressions of nm23 gene products/nucleoside diphosphate kinas...

A high percentage of human breast and ovarian tumors display amplified c-erbB-2 gene copies, leading to overexpression of the growth factor receptor. Its membrane location and elevated expression make the erbB-2 protein an appropriate target for a directed tumor therapy. We have used recombinant DNA technology to produce a single-chain antibody-exotoxin A (scFv-ETA) fusion protein which specifi...

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...

ErbB-4 is a recently discovered member of the class I receptor tyrosine kinase family (ErbB). Little is known about its expression and its importance in human malignancy. To delineate the biological function of ErbB-4 receptors in breast cancer, we used a hammerhead ribozyme strategy to achieve down-regulation of ErbB-4 receptors in various breast cancer cell lines. We observed that down-regula...

The overexpression of members of the ErbB tyrosine kinase receptor family has been associated with cancer progression. We demonstrate that focal adhesion kinase (FAK) is essential for oncogenic transformation and cell invasion that is induced by ErbB-2 and -3 receptor signaling. ErbB-2/3 overexpression in FAK-deficient cells fails to promote cell transformation and rescue chemotaxis deficiency....

Exposure of tumor cells to ionizing radiation causes compensatory activation of multiple intracellular survival signaling pathways to maintain viability. In human carcinoma cells, radiation exposure caused an initial rapid inhibition of protein tyrosine phosphatase function and the activation of ERBB receptors and downstream signaling pathways. Radiation-induced activation of extracellular regu...

Hypothalamic astroglial erbB tyrosine kinase receptors are required for the timely initiation of mammalian puberty. Ligand-dependent activation of these receptors sets in motion a glia-to-neuron signaling pathway that prompts the secretion of luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling sexual development, from hypothalamic neuroendocrine neurons. The neuronal syst...

The ErbB-2/HER-2 receptor tyrosine kinase is overexpressed in a wide range of solid human tumors. The ErbB-2 gene product is a transmembrane glycoprotein belonging to the epidermal growth factor receptor family, and its cytoplasmic domain is responsible for sending the mitogenic signals into cells. We discovered that this domain of ErbB-2 interacts with Tid1 protein, the human counterpart of th...

To assess the importance of Neu activation during mammary tumorigenesis, altered receptors harboring in-frame deletions within the extracellular domain were expressed in transgenic mice. Females from several independent lines develop multiple mammary tumors that frequently metastasize to the lung. Tumor progression in these strains was associated with elevated levels of tyrosine-phosphorylated ...