Prior studies in breast cancer cells have shown that lapatinib and obatoclax interact in a greater than additive fashion to cause cell death and do so through a toxic form of autophagy. The present studies sought to extend our analyses to the central nervous system (CNS) tumor cells and to further define mechanisms of drug action. Lapatinib and obatoclax killed multiple CNS tumor isolates. Cell...

The three oncogenes, ErbB receptors, Ras proteins and nucleolin may contribute to malignant transformation. Previously, we demonstrated that nucleolin could bind both Ras protein and ErbB receptors. We also showed that the crosstalk between the three proteins facilitates anchorage independent growth and tumor growth in nude mice, and that inhibition of this interaction in prostate and colon can...

PURPOSE Non-small cell lung cancer (NSCLC) is usually associated with a poor prognosis. Some patients survive their disease, and the underlying molecular mechanisms are still poorly understood. The purpose of this investigation was to evaluate expression profiles of proteins determining the survival of NSCLC patients for 5 years. EXPERIMENTAL DESIGN The expression of 21 gene products was eval...

The estrogen receptor alpha (ERalpha), progesterone receptor (PR), and erbB2 (Her2 in humans) are important prognostic markers of human breast cancer, and they are variably expressed in different subtypes of breast cancer. The basal subtype, for example, is negative for ERalpha, PR, and Her2 by immunohistochemistry. We investigated the expression of these signaling molecules in enriched populat...

We propose a new mechanism to explain autoinhibition of the epidermal growth factor receptor (EGFR/ErbB) family of receptor tyrosine kinases based on a structural model that postulates both their juxtamembrane and protein tyrosine kinase domains bind electrostatically to acidic lipids in the plasma membrane, restricting access of the kinase domain to substrate tyrosines. Ligand-induced dimeriza...

We previously found that some myeloma cell lines express the heparin-binding epidermal growth factor-like growth factor (HB-EGF) gene. As the proteoglycan syndecan-1 is an HB-EGF coreceptor as well as a hallmark of plasma cell differentiation and a marker of myeloma cells, we studied the role of HB-EGF on myeloma cell growth. The HB-EGF gene was expressed by bone marrow mononuclear cells of 8/8...

erbB receptors contribute to tumor formation and progression. Variable expression of erbB1, erbB2, and erbB3 has been reported in nevi and melanomas; erbB4 has hardly been investigated. We examined the expression of all 4 erbB receptors in common and dysplastic nevi and melanomas. Formalin-fixed, paraffin-embedded tissues of 100 melanomas, 27 common nevi, and 23 dysplastic nevi were immunostain...

Consistent with the hypothesis that neuroinflammatory processes contribute to the neuropathology of schizophrenia, the protein levels of epidermal growth factor (EGF) and its receptor ErbB1 are abnormal in patients with schizophrenia. To evaluate neuropathological significance of this abnormality, we established an animal model for behavioral deficits by administering EGF into the striatum and ...