Kettering University

About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: Cancer & RNA. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.

Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer

Abstract: PurposeTreatment with programmed cell death-1 or programmed death ligand 1 (PD-(L)1) inhibitors is now standard therapy for patients with lung cancer. The immunosuppressive effect of corticosteroid...

Crystal-structure of the phosphotyrosine recognition domain sh2 of v-src complexed with tyrosine-phosphorylated peptides

Abstract: Three-dimensional structures of complexes of the SH2 domain of the v-src oncogene product with two phosphotyrosyl peptides have been determined by X-ray crystallography at resolutions of 1.5 and 2.0 A, respectively. A central antiparallel β-sheet in the structure is flanked by two α-helices, with peptide binding mediated by the sheet, intervening loops and one of the helices. The specific recognition of phosphotyrosine involves amino–aromatic interactions between lysine and arginine side chains and the ring system in addition to hydrogen-bonding interactions with the phosphate.

Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.

Abstract: Pier Paolo Pandolfi and colleagues report that prostate-specific overexpression of ERG in transgenic mice results in no overt phenotype on its own but promotes progression of intraepithelial neoplasia to adenocarcinoma in a PTEN heterozygous background. They also find that human TMPRSS2-ERG–positive tumors are enriched for PTEN loss, suggesting that these two events cooperate in human prostate tumorigenesis. Chromosomal translocations involving the ERG locus are frequent events in human prostate cancer pathogenesis; however, the biological role of aberrant ERG expression is controversial1. Here we show that aberrant expression of ERG is a progression event in prostate tumorigenesis. We find that prostate cancer specimens containing the TMPRSS2-ERG rearrangement are significantly enriched for loss of the tumor suppressor PTEN. In concordance with these findings, transgenic overexpression of ERG in mouse prostate tissue promotes marked acceleration and progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to prostatic adenocarcinoma in a Pten heterozygous background. In vitro overexpression of ERG promotes cell migration, a property necessary for tumorigenesis, without affecting proliferation. ADAMTS1 and CXCR4, two candidate genes strongly associated with cell migration, were upregulated in the presence of ERG overexpression. Thus, ERG has a distinct role in prostate cancer progression and cooperates with PTEN haploinsufficiency to promote progression of HGPIN to invasive adenocarcinoma.