Loading...
Please wait, while we are loading the content...
Similar Documents
A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | McCallum, Lynn Price, Susan Planque, Nathalie Perbal, Bernard Pierce, Andrew Irvine, Alexandra Elizabeth |
| Copyright Year | 2006 |
| Abstract | Chronic myeloid leukemia (CML) is characterized by the presence of the constitutively active BCR-ABL protein tyrosine kinase. Using a multipotent hemopoietic cell line, FDCP-Mix, expressing BCR-ABL tyrosine kinase, we investigated the initial effects of this kinase in primitive hematopoietic stem cells. We identified down-regulation of a novel gene, CCN3, as a direct consequence of BCR-ABL kinase activity. CCN3 has been reported to function as a tumor suppressor gene in solid tumors. Northern and Western blotting plus immunocytochemical analysis confirmed CCN3 expression is decreased and is tyrosine-phosphorylated in BCR-ABL kinase active FDCP-Mix cells. Decreased cellular CCN3 correlated with increased CCN3 secretion in BCR-ABL kinase active cells. In vitro treatment of human CML cell lines with imatinib or siRNA directed against BCR-ABL significantly reduced BCR-ABL while increasing CCN3 expression. Cells from patients responding to imatinib showed a similar decrease in BCR-ABL and increase in CCN3. CML CD34+ cells treated with imatinib in vitro demonstrated increased CCN3 protein. Transfecting CCN3 into BCR-ABL+ cells inhibited proliferation and decreased clonogenic potential. CCN3 plays an important role in internal and external cell-signaling pathways. Thus, BCR-ABL can regulate protein levels by governing secretion, a novel mechanism for this tyrosine kinase. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/108/5/1716.full.pdf?sso-checked=true |
| PubMed reference number | 16670264v1 |
| Volume Number | 108 |
| Issue Number | 5 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | B-Cell Receptor Complex BCR gene BCR protein, human BCR/ABL1 Fusion Protein with ABL1 NP_005148.2:p.T315I Biospecimen Core Resource Facility Cell Differentiation process Down-Regulation Fusion Proteins, bcr-abl Hematopoietic stem cells Leukemia, Myelocytic, Acute Myeloid Leukemia Myeloid Leukemia, Chronic NOV gene NOV wt Allele Neoplasms Nephroblastoma Overexpressed Protein Patients Protein Tyrosine Kinase Tumor Suppressor Genes Western Blotting abl Oncogene imatinib solid tumor |
| Content Type | Text |
| Resource Type | Article |
