Sentences with phrase «abl gene»

The Abl gene expresses a membrane - associated protein, a tyrosine kinase, and the BCR - Abl transcript is also translated into a tyrosine kinase.

To evaluate whether altered expression of the ABL genes is associated with breast cancer progression and metastasis, we examined the expression of ABL1 and ABL2 in normal and invasive breast tumor specimens using published TCGA (The Cancer Genome Atlas) data sets (14 — 16).

Not exact matches

In experiments on cell cultures, both of these inhibitors succeeded in breaking various forms of the TKI resistance: including forms caused by additional mutations of the gene Bcr - Abl as well as those caused by large quantities of the protein Gab2.

One of these disrupted genes is called BCR - ABL and drugs that target this mutation have transformed the treatment of CML.

The activity of tyrosine kinases is typically regulated in an auto - inhibitory fashion, but the BCR - Abl fusion gene codes for a protein that is «always on» or continuously activated leading to unregulated cell division (i.e. cancer).

This gene encodes for a Bcr - abl fusion protein.

Previous reports have shown that in a genetic abnormality called Philadelphia chromosome, fusion of ABL and BCR genes cause leukemia.

In addition to inhibiting STAT5 signaling, we found that depletion of ABL kinases decreased the expression of the Hippo pathway mediator TAZ and downstream target genes in triple - negative and HER2 + breast cancer cells.

We found that depletion of the ABL kinases decreased TAZ binding to some of its target genes (fig.

ABL kinases regulate the expression of genes in the JAK / STAT and Hippo pathway signatures in metastatic breast cancer cells.

We showed that inactivation of the ABL kinases in breast cancer cells resulted in decreased expression of genes in the JAK / STAT and cytokine / cytokine receptor pathway signatures, which may be due to decreased STAT5A mRNA expression and reduced STAT5 phosphorylation in ABL1 / ABL2 - depleted breast cancer cells.

Inactivation of ABL kinases inhibited the expression of the TAZ target gene AXL, which shows increased expression in several human cancers and correlates with poor prognosis, increased invasiveness and metastasis, and enhanced drug resistance (53, 54).

Further, we identified a role for ABL kinases in promoting the expression of multiple pro — bone metastasis genes such as AXL (which encodes a receptor tyrosine kinase), IL6 (which encodes interleukin - 6), MMP1 (which encodes matrix metalloproteinase 1), and TNC (which encodes tenascin - C) through TAZ - and signal transducer and activator of transcription 5 (STAT5)-- mediated signaling.

We found that inactivation of the ABL kinases in breast cancer cells also decreased STAT5A mRNA and downstream expression of STAT5 target genes, including TNC (Fig. 6D).

Further, inactivation of the ABL kinases resulted in decreased expression of the genes in the Hippo, Janus kinase (JAK) / STAT, and cytokine / cytokine receptor pathway signatures (Fig. 6B).

To identify key molecular mediators of the ABL kinases implicated in the regulation of the ABL1 / ABL2 - dependent pathways, we analyzed the expression of individual genes for transcripts altered by loss of the ABL kinases.

However, we can not rule out the possibility that ABL kinases might regulate YAP1 - mediated expression of other target genes in breast cancer cells.

These mutant kinases are attractive therapeutic targets, as demonstrated by the efficacy of imatinib in BCR - ABL — positive chronic myelogenous leukemia (CML), 5 as well as in MPD associated with activating alleles involving PDGFRA or PDGFRB.2, 6,7 In addition, activating mutations in the FLT3 receptor tyrosine kinase are the most common genetic event in acute myeloid leukemia (AML), and specific inhibitors of the FMS - like tyrosine kinase 3 (FLT3) have entered late - stage clinical trials.8 Although mutations in tyrosine kinases and in other genes have been identified in a subset of MPD and AML, in many cases the genetic events that contribute to the molecular pathogenesis of these diseases remain unknown.

In breast cancer cells, the ABL kinases activated the transcriptional coactivator TAZ and the transcription factor STAT5, which triggered the transcription of genes encoding factors that activate osteoclasts (cells that break down bone) and those that enhance the survival of breast cancer cells in the bone microenvironment.