Despite the ongoing "war on cancer," cancer remains one of the major causes of human morbidity and mortality. A new paradigm of targeted therapies holds the most promise for the future, making identification of tumor-specific therapeutic targets of prime importance. ERBB2/HER2, best known for its role in breast cancer tumorigenesis, can be targeted by two types of pharmacological manipulation: ...

Activation of the ErbB2 receptor tyrosine kinase stimulates breast cancer cell migration. Cell migration is a complex process that requires the synchronized reorganization of numerous subcellular structures including cell-to-matrix adhesions, the actin cytoskeleton and microtubules. How the multiple signaling pathways triggered by ErbB2 coordinate, in time and space, the various processes invol...

A causal role has been inferred for ERBB2 overexpression in the etiology of breast cancer and other epithelial malignancies. The development of therapeutics that inhibit this tyrosine kinase cell surface receptor remains a high priority. This report describes the specific downregulation of ERBB2 protein and mRNA in the breast cancer cell line SK-BR-3 by using antisense DNA phosphorothioates. An...

Objective: Diabetes is heterogeneous group of disorders characterized by aberrant insulin signaling and hyperglycmia. Chronic hypergylcemia leads to the development of complications including diabetic peripheral neuropathy (DPN). DPN is a pervasive complication associated with diabetes and its development is not completely understood. Research Design and Methods: We aimed to determine if ErbB2 ...

Medulloblastoma is frequently disseminated throughout the central nervous system by the time of diagnosis. Conventional therapeutic approaches have not reduced the high mortality associated with metastatic medulloblastoma and little is known regarding the molecular mechanisms that promote tumor invasion. Previously, we reported that overexpression of ERBB2 in medulloblastoma is associated with ...

Metformin is an oral biguanide used for type II diabetes. Epidemiologic studies suggest a link between metformin use and reduced risk of breast and other types of cancers. ErbB2-expressing breast cancer is a subgroup of tumors with poor prognosis. Previous studies demonstrated that metformin is a potent inhibitor of ErbB2-overexpressing breast cancer cells; metformin treatment extends the life ...

While most breast cancers are thought to arise from the luminal layer of the breast tissue, it remains unclear which specific cells in the luminal layer are the cells of origin of breast cancer. We have previously reported that WAP-positive luminal epithelial cells are at increased susceptibility to tumor initiation by ErbB2 compared to the bulk population, while the mammary cells with canonica...

Aberrant expression or activity of epidermal growth factor receptor (EGFr) or the closely related p185(erbB2) can promote cell proliferation and survival and thereby contribute to tumorigenesis. Specific antibodies and low molecular-weight tyrosine kinase inhibitors of both proteins are in clinical trials for cancer treatment. CP-654577 is a potent inhibitor selective for p185(erbB2), relative ...

Human breast cancer cell line SKBR3 expresses high level of the ErbB2 molecule, which has been associated with poor prognosis of breast cancer. Elevated ErbB2 functions as a transactivating co-receptor and promotes the formation of ErbB2 containing heterodimers, which are more mitogenic and transforming, and have a higher ligand affinity and signaling potency by virtue of the potent latent kina...