Abstract: A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNk Characterization of the cloned DNA fragment mapped the region of v-erbB homology to three exons with closest homology of 64% and 67% to a contiguous region within the tyrosine kinase domains of the EGFR and erbB-2 proteins, respectively. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was mapped to human chromosome 12q11-13 and was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies.

Abstract: Disccoveries are disclosed that show particular aspects of recombinant DNA technology can be used sucessfully to produce hitherto unknown human keratinocyte growth factor (KGF) protein free of other polypeptides. These proteins can be produced in various functional forms from spontaneously secreting cells or from DNA segments introduced into cells. These forms variously enable biochemical and functional studies of this novel protein as well as production of antibodies. Means are described for determining the level of expression of genes for the KGF protein, for example, by measuring mRNA levels in cells or by measuring antigen secreted in extracellular or body fluids.

Abstract: Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used successfully to produce a hitherto unknown type of human Platelet-Derived Growth Factor (PDGF) receptor protein free of other PDGF receptors. These proteins can be produced from DNA segments in cells in various functional forms. These forms variously enable biochemical and functional studies of these novel receptors as well as production of antibodies. Means are described for determining the level of expression of genes for specific types of PDGF receptor proteins, for example, by measuring mRNA in cells with PDGF receptor type-specific DNA probes or by measuring antigen in biological samples with type-specific antibodies.

Abstract: The isolation, cloning and characterization of a human gene related to but distinct from the EGF receptor gene has been described. Nucleotide sequence of the gene and amino acid sequence of the polypeptide encoded by the gene have been determined. The use of the nucleic acid probes and antibodies having specific binding affinity with said polypeptide for diagnostic and therapeutic purposes has also been described.

Abstract: A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. Characterization of the cloned DNA fragment mapped the region of v-erbB homology to three exons with closest homology of 64% and 67% to a contiguous region within the tyrosine kinase domains of the EGFR and erbB-2 proteins, respectively. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was mapped to human chromosome 12q11-13 and was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies.

Abstract: The invention provides a novel, secreted protein that contains a region homologous to ligand binding domain of a cytokine receptor. This protein, called Frizzled-related protein (FRP), antagonizes the signaling of the Wnt family of cytokines. Extracellular signaling molecules such as the Wnt family members have essential roles as inducers of cellular proliferation, migration, differentiation, and tissue morphogenesis. As Wnt molecules are known to participate in the aberrant growth associated with neoplasia, Wnt antagonists such as FRP are valuable tools which both for understanding oncogenesis and for the design of new cancer therapies.

Abstract: The present invention relates to a novel truncated forms of hepatocyte growth factor (HGF) which specifically antagonizes the activity of HGF and to a novel truncated form of HGF that is a partial HGF agonist. In particular, the present invention relates to the purification, molecular cloning, recombinant expression of the truncated HGF variants and related pharmaceutical compositions.

Abstract: The present invention relates to a novel truncated forms of hepatocyte growth factor (HGF) which specifically antagonizes the activity of HGF and to a novel truncated form of HGF that is a partial HGF agonist. In particular, the present invention relates to the purification, molecular cloning, recombinant expression of the truncated HGF variants and related pharmaceutical compositions. The present invention further relates to the utilization of the small HGF variants to either inhibit HGF mitogenesis or stimulate HGF mitogenesis in cells expressing the receptor for HGF.

Abstract: The present invention relates to methods for modulating the migratory, invasive and metastatic properties of cells expressing N-cadherin for the treatment of proliferative disorders including, but not limited to, cancers such as melanomas, breast, and prostate cancer. The invention further relates to drug screening assays designed to identify compounds that modulate N-cadherin activity and the use of such compounds in the treatment of disorders involving N-cadherin modulated cell migration, invasion, and metastasis. The invention also relates to methods for diagnosis and prognosis of disorders such as cancer that rely on detection of N-cadherin expression levels. The invention is based on the discovery that N-cadherin expression increases the migratory, invasive and metastatic properties of cells. It is additionally based on the discovery that increased N-cadherin expression sensitizes cells to growth factors such as FGF-2 and increases matrix metalloproteinase-9 (MMP-9) accumulation.

Abstract: The invention provides a novel, secreted protein that contains a region homologous to ligand binding domain of a cytokine receptor. This protein, called Frizzled-related protein (FRP), antagonizes the signaling of the Wnt family of cytokines. Extracellular signaling molecules such as the Wnt family members have essential roles as inducers of cellular proliferation, migration, differentiation, and tissue morphogenesis. As Wnt molecules are known to participate in the aberrant growth associated with neoplasia, Wnt antagonists such as FRP are valuable tools which both for understanding oncogenesis and for the design of new cancer therapies.

Abstract: Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used sucessfully to produce hitherto unknown human keratinocyte growth factor (KGF) protein free of other polypeptides. These proteins can be produced in various functional forms from spontaneously secreting cells or from DNA segments introduced into cells. These forms variously enable biochemical and functional studies of this novel protein as well as production of antibodies. Means are described for determining the level of expression of genes for the KGF protein, for example, by measuring mRNA levels in cells or by measuring antigen secreted in extracellular or body fluids.

Abstract: The high affinity which is characteristic of homodimers of IgG heavy chains is achieved, along with favorable secretion and flexibility/adaptability properties, in a fusion protein that has a nonantibody portion, comprised of an effector domain, joined to the aminoterminal end of an IgG-derived sequence consisting of a hinge:CH2:CH3 segment which lacks a CH1 domain, with a heterologous signal peptide preferably provided upstream of the nonantibody portion. Chimeric molecules of this structure can be secreted readily in stable form by mammalian cells transfected with DNA encoding the molecule, and are amenable to rapid, efficient purification to homogeneity, for example, using protein A. These molecules are effective substitutes for monoclonal antibodies in contexts such as flow cytometry, immunohistochemistry, immunoprecipitation and ELISAs. A fusion protein as described also can be used in screening for agonists and antagonists to the cognate binding partner of the nonantibody portion of the fusion protein.

Abstract: Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used successfully to produce a hitherto unknown type of human Platelet-Derived Growth Factor (PDGF) receptor protein free of other PDGF receptors. These proteins can be produced from DNA segments in cells in various functional forms. These forms variously enable biochemical and functional studies of these novel receptors as well as production of antibodies. Means are described for determining the level of expression of genes for specific types of PDGF receptor proteins, for example, by measuring mRNA in cells with PDGF receptor type-specific DNA probes or by measuring antigen in biological samples with type-specific antibodies.

Abstract: Recombinant DNA technology was used to clone encoding nucleic acids for the human alpha platelet-derived growth factor receptor (PDGF-R type alpha). Peptides corresponding to the predicted sequence of this type and of the PDGF-R type beta were used to elicit antibodies specific for either type of the PDGF-R. Immunoassays are described for determining the level of PDGF-R type alpha in biological samples with the PDGF-R type alpha-specific antibodies.

Abstract: The present invention relates to a potent mitogenic growth factor called plasminogen-like growth factor (PLGF) isolated from conditioned medium of human lung fibroblasts. The protein has an apparent molecular weight under reducing conditioning of 87 kDa and is structurally related to hepatocyte growth factor (HGF); however unlike HGF, which appears to be specific for hepatic cells, PLGF stimulates a wide spectrum of target cells including melanocytes, endothelial cells and epithelial cells but excludes fibroblast cells. The present invention further relates to recombinant cloned DNA fragments and expression cell systems expressing biologically active PLGF. The availability of purified PLGF as well as immunological and molecular probes should facilitate the study of proliferative disorders in which the factor plays an important role.

Abstract: The isolation, cloning and characterization of a human gene related to but distinct from the EGF receptor gene has been described. Nucleotide sequence of the gene and amino acid sequence of the polypeptide encoded by the gene have been determined. The use of the nucleic acid probes and antibodies having specific binding affinity with said polypeptide for diagnostic and therapeutic purposes has also been described.

Abstract: Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used successfully to produce a hitherto unknown type of human Platelet-Derived Growth Factor (PDGF) receptor protein free of other PDGF receptors. These proteins can be produced from DNA segments in cells in various functional forms. These forms variously enable biochemical and functional studies of these novel receptors as well as production of antibodies. Means are described for determining the level of expression of genes for specific types of PDGF receptor proteins, for example, by measuring mRNA in cells with PDGF receptor type-specific DNA probes or by measuring antigen in biological samples with type-specific antibodies.

Abstract: A DNA fragment distinct from the epidermal growth factor receptor (EGFR) and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. cDNA cloning revealed a predicted 148 kd transmembrane polypeptide with structural features identifying it as a member of the erbB family, prompting designation of the new gene as erbB-3. It was shown to be expressed as a 6.2 kb transcript in a variety of normal tissues of epithelial origin. Markedly elevated erbB-3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings indicate that increased erbB-3 expression, as in the case of EGFR and erbB-2, plays a role in some human malignancies. Using erbB-3 specific antibodies (polyclonal or monoclonal), the erbB-3 protein was identified as a 180 kDa glycoprotein, gp180.sup.erbB-3. The intrinsic catalytic function of gp180.sup.erbB-3 was uncovered by its ability to autophosphorylate in vitro.

Abstract: Potent neutralizing monoclonal antibodies to the human .alpha. PDGF receptor (.alpha. PDGFR) and fragments thereof are described. These monoclonal antibodies specifically bind to an epitope on .alpha. PDGFR, inhibits PDGF binding with PDGF, antagonizes PDGF, and does not bind .beta. PDGFR receptor. A hybridoma cell line producing such a monoclonal antibody, methods of in vivo imaging of a pathological conditions and methods of inhibiting the growth of a neoplasia expressing .alpha. PDGFR, which use these monoclonal antibodies are also described. In vitro assays for detecting the presence of .alpha. PDGFR and for evaluating the binding affinity of a test compound are also described.

Abstract: Potent neutralizing monoclonal antibodies to the human .alpha. PDGF receptor (.alpha. PDGFR) and fragments thereof are described. These monoclonal antibodies specifically bind to an epitope on .alpha. PDGFR, inhibits PDGF binding with PDGF, antagonizes PDGF, and does not bind .beta. PDGFR receptor. A hybridoma cell line producing such a monoclonal antibody, methods of in vivo imaging of a pathological conditions and methods of inhibiting the growth of a neoplasia expressing .alpha. PDGFR, which use these monoclonal antibodies are also described. In vitro assays for detecting the presence of .alpha. PDGFR and for evaluating the binding affinity of a test compound are also described.