Autocrine secretion of osteopontin results in degradation of I kappa B in Bcr-Abl-expressing cells.

Br J Haematol 2005 Mar;128(5):711-21

Cell Development and Disease Laboratory, Department of Biochemistry, BioSciences Institute, University College Cork, Cork, Ireland.

Osteopontin has been identified as a marker of metastasis formation and its increased expression has been correlated with the malignancy of cancer. In this study we provide evidence that increased expression of osteopontin may also be associated with progression of Bcr-Abl-expressing leukaemia cells. The Bcr-Abl fusion protein, generated by the Philadelphia translocation, is the hallmark of chronic myeloid leukaemia (CML). CML exhibits clinically distinct phases. Advanced disease shows defective differentiation, bone marrow infiltration and drug resistance. The critical signalling mediating this disease progression is unknown. Increased aggressiveness of the disease has been correlated with elevated amounts of Bcr-Abl. We generated a 32D cell line model to study the consequences of different expression levels of Bcr-Abl. Osteopontin was identified by microarray analysis as highly upregulated in cells expressing elevated amounts of Bcr-Abl. Moreover, in high Bcr-Abl expressing cells, an additional 50 kDa isoform of osteopontin was detected. It was found that this protein was secreted and that myeloid progenitor cells also expressed appropriate receptors for autocrine activation. We demonstrated that secretion of osteopontin resulted in enhanced degradation of I kappa B, the inhibitor of NF-kappa B. These data indicate a novel consequence of elevated Bcr-Abl expression, which may contribute to the progression of CML.

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2141.2004.05355.xDOI Listing
March 2005
2 Reads

Publication Analysis

Top Keywords

increased expression
8
osteopontin identified
8
amounts bcr-abl
8
degradation kappa
8
secretion osteopontin
8
elevated amounts
8
osteopontin
6
bcr-abl
6
cells
5
model study
4
cell model
4
32d cell
4
bcr-abl generated
4
study consequences
4
generated 32d
4
bcr-abl osteopontin
4
analysis highly
4
highly upregulated
4
upregulated cells
4
microarray analysis
4

References

(Supplied by CrossRef)

Behrend E.I. et al.
Cancer Research 1994

Chang P.L. et al.
Annals of the New York Academy of Sciences 1995

Flamant S. et al.
Blood 2003

Similar Publications