Transformation by the v-sis oncogene appears to require an interaction of its protein product, p28v-sis, with the receptor for the platelet-derived growth factor (PDGF). However, this interaction may not occur at the cell surface as predicted by the autocrine hypothesis because phenotypic transformation was not reversed by incubation of SSV-NRK cells with antisera to PDGF and because morphological transformation did not occur when nontransformed NRK cells were cultured continuously with p28v-sis. A mutant of the wild-type v-sis gene was constructed that encodes a v-sis protein targeted for retention within the endoplasmic reticulum and Golgi. NRK cells expressing the mutant v-sis gene did not secrete any detectable v-sis protein but were as fully transformed as wild-type v-sis transfectants. The results support a mechanism of transformation by v-sis in which internal activation of the PDGF receptor occurs before expression of either p28v-sis or the PDGF receptor at the cell surface.
NF-kappaB is a family of transcription factors that have been shown to be elevated in a variety of tumor types and in some cases central to their survival and growth. Here we present evidence that U-87 MG and U-118 MG growth is regulated by NF-kappaB and controlled by PDGF. NF-kappaB activity was suppressed by a dominant negative mutant of the human PDGF type beta receptor and PDGF-B chain neutralizing antibodies. Creation of cell lines that had inducible expression of shRNAs directed against either c-Rel or RelA inhibited growth almost 90% indicating that NF-kappaB plays a central role in glioblastoma growth.
The Assay Guidance Manual (AGM) is an eBook of best practices for the design, development, and implementation of robust assays for early drug discovery. Initiated by pharmaceutical company scientists, the manual provides guidance for designing a “testing funnel” of assays to identify genuine hits using high‐throughput screening (HTS) and advancing them through preclinical development. Combined with a workshop/tutorial component, the overall goal of the AGM is to provide a valuable resource for training translational scientists.
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