Search results for "Human fibroblast"

Aneuploid IMR90 cells induced by depletion of pRB, DNMT1 and MAD2 show a common gene expression signature

2019

Chromosome segregation defects lead to aneuploidy which is a major feature of solid tumors. How diploid cells face chromosome mis-segregation and how aneuploidy is tolerated in tumor cells are not completely defined yet. Thus, an important goal of cancer genetics is to identify gene networks that underlie aneuploidy and are involved in its tolerance. To this aim, we induced aneuploidy in IMR90 human primary cells by depleting pRB, DNMT1 and MAD2 and analyzed their gene expression profiles by microarray analysis. Bioinformatic analysis revealed a common gene expression profile of IMR90 cells that became aneuploid. Gene Set Enrichment Analysis (GSEA) also revealed gene-sets/pathways that are …

The synthesis of SNAT2 transporters is required for the hypertonic stimulation of system A transport activity

2004

AbstractIn cultured human fibroblasts incubated under hypertonic conditions, the stimulation of system A for neutral amino acid transport, associated to the increased expression of the mRNA for SNAT2 transporter, leads to an expanded intracellular amino acid pool and to the recovery of cell volume. A protein of nearly 60 kDa, recognized by an antiserum against SNAT2, is increased both in the pool of biotinylated membrane proteins and in the total cell lysate of hypertonically stressed cells. The increased level of SNAT2 transporters in hypertonically stressed cells is confirmed by immunocytochemistry. DRB, an inhibitor of transcription, substantially inhibits the increase of SNAT2 proteins …

ALS-Related Mutant FUS Protein Is Mislocalized to Cytoplasm and Is Recruited into Stress Granules of Fibroblasts from Asymptomatic FUS P525L Mutation…

2017

Background: Amyotrophic lateral sclerosis (ALS) shows a strong genetic basis, with SOD1, FUS, TARDBP, and C9ORF72 being the genes most frequently involved. This has allowed identification of asymptomatic mutation carriers, which may be of help in understanding the molecular changes preceding disease onset. Objectives: We studied the cellular expression of FUS protein and the effect of heat-shock-and dithiothreitol-induced stress in fibroblasts from FUS P525L mutation carriers, healthy controls, and patients with sporadic ALS. Methods: Western blots and immunocytochemistry were performed to study the subcellular localization of FUS protein. Control and stressed cells were double stained with…

Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy

2016

AbstractInactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criter…

ALS-RELATED FUS PROTEIN IS MISLOCALIZED TO CYTOPLASM AND RECRUITED INTO STRESS GRANULES IN FIBROBLASTS OF ASYMPTOMATIC FUS P525L MUTATION CARRIERS

Symptoms onset in Amyotrophic Lateral Sclerosis (ALS) occur when over 70% of motor neurons is already lost, suggesting a relatively long pre-symptomatic phase. The description of several genes linked to ALS (e.g., SOD1, FUS, TARDP, C9orf72) has now allowed identification of pre-symptomatic carriers. These pre-symptomatic (or even preclinical) carriers can be followed up with the aim to identify the very early clinical disease-related changes or a valuable biomarker. These efforts seem at present the best approach for the implementation of an early symptomatic therapy or for the disease prevention. In this work, we studied the expression of FUS protein in cultured skin fibroblasts from pre-s…