KLF6 Gene and early melanoma development in a collagen I-rich extracellular environment.

Background: A putative tumor suppressor gene at chromosome 10p15, which contains KLF6 and other genes, is predicted to be lost during melanoma development, and its identity is unknown. In this study, we investigated the biological roles and identity of this tumor suppressor gene.

Methods: The human UACC 903 melanoma cell line containing introduced DNA fragments from the 10p15 region with (10E6/3, 10E6/11, and 10E6/18) and without (10ER4S.

A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor.

Epidermal growth factor receptor (EGFR) has attracted considerable attention as a target for cancer therapy. Wild-type (wt)EGFR is amplified/overexpressed in a number of tumor types, and several mutant forms of the coding gene have been found, with DeltaEGFR, a deletion mutation lacking exons 2-7 of the external domain, being the most common and particularly associated with glioblastoma. We generated monoclonal antibodies (mAbs) against NR6(DeltaEGFR) (mouse fibroblast line NR6 transfected with DeltaEGFR).

Mutant epidermal growth factor receptor signaling down-regulates p27 through activation of the phosphatidylinositol 3-kinase/Akt pathway in glioblastomas.

Alterations of the epidermal growth factor receptor (EGFR) gene are common in some forms of cancer and the most frequent is a deletion of exons 2-7. We have previously shown that this mutant receptor, called DeltaEGFR, confers enhanced tumorigenicity to glioblastoma cells through elevated proliferation and reduced apoptotic rates of the tumor cells in vivo. To understand the molecular mechanisms that underlie DeltaEGFR-enhanced proliferation, we examined the gene products that control cell cycle progression.

A novel seven transmembrane receptor induced during the early steps of astrocyte differentiation identified by differential expression.

The rat glial progenitor cell line CG-4 can be induced to differentiate into either oligodendrocytes or type-2 astrocytes. In order to identify genes whose expression varies coincident with such phenotypic differentiation, we employed representational difference analysis (RDA) of mRNA. Here, we report 38 cDNAs induced in type-2 astrocytes, oligodendrocytes, or both differentiated states.

Novel monoclonal antibody specific for the de2-7 epidermal growth factor receptor (EGFR) that also recognizes the EGFR expressed in cells containing amplification of the EGFR gene.

In some respects, the EGFR appears to be an attractive target for tumor-targeted antibody therapy: it is overexpressed in many types of epithelial tumor and inhibition of signaling often induces an anti-tumor effect. The use of EGFR specific antibodies, however, may be limited by uptake in organs that have high endogenous levels of the wild type EGFR such as the liver. The de2-7 EGFR (or EGFRvIII) is a naturally occurring extracellular truncation of the EGFR found in a number of tumor types including glioma, breast, lung and prostate.

CD95-mediated apoptosis of human glioma cells: modulation by epidermal growth factor receptor activity.

The death ligands CD95L and Apo2L/TRAIL are promising investigational agents for the treatment of malignant glioma. EGFR is overexpressed in a significant proportion of malignant gliomas in vivo. Here, we report that CD95L-induced cell death is enhanced by EGFR inhibition using tyrphostine AG1478 in 7 of 12 human malignant glioma cell lines.

Causes of drug resistance and novel therapeutic opportunities for the treatment of glioblastoma.

Malignant gliomas are among the most lethal and intractable of human tumors and drug resistance is one of the major obstacles to their successful treatment. Recent advances in the molecular biology and genetics of human cancers provide a detailed understanding of cellular and molecular responses to chemotherapy and how drug resistance may develop. Several oncogenes and tumor suppressor genes have been shown to confer resistance to tumor cells and should, therefore, provide novel and defined targets for cancer treatment.