Prostate apoptosis response gene-4 (par-4) abrogates the survival function of p185(BCR-ABL) in hematopoietic cells

Kukoc-Zivojnov, Natasa, Puccetti, Elena, Chow, Kai U, Bergmann, Marion, Ruthardt, Martin ORCID: https://orcid.org/0000-0003-1021-3811, Hoelzer, Dieter, Mitrou, Paris S, Weidmann, Eckhart and Boehrer, Simone 2004. Prostate apoptosis response gene-4 (par-4) abrogates the survival function of p185(BCR-ABL) in hematopoietic cells. Experimental Hematology 32 (7) , pp. 649-656. 10.1016/j.exphem.2004.04.004

Full text not available from this repository.

Abstract

Objective Prostate apoptosis response gene-4 (par-4) is deregulated in acute and chronic lymphatic leukemia. Given its pro-apoptotic role in neoplastic lymphocytes and evidence that par-4 antagonizes oncogenic Ras in solid tumors, we hypothesized that par-4 may act as a tumor suppressor impairing transformation induced by p185BCR-ABL. Materials and Methods The capacity of par-4 to interfere with factor independence induced by p185BCR-ABL and V12ras was evaluated by analysis of factor-independent growth of p185BCR-ABL/ par-4 and V12ras/par-4 tranduced cells. The expression of par-4 and p185BCR-ABL by the respective constructs was controlled by Western blot analysis. Activated Ras was detected by pull-down assay in the cell clones expressing p185BCR-ABL in the absence and presence of par-4. Results Expression of p185BCR-ABL causes factor independence, signifying a conversion toward a transformed phenotype in hematopoietic precursors. We demonstrate that par-4 completely abolishes factor independence induced by p185BCR-ABL and partially abrogates factor independence caused by activated V12ras. Evaluating the underlying molecular mechanisms, we show that par-4 hinders activation of oncogenic Ras and causes concomitant disruptions of p185BCR-ABL-mediated signaling. Conclusion We provide the first evidence that par-4 exhibits an antitransforming capacity by antagonizing p185BCR-ABL-induced factor-independent proliferation in hematopoietic cells.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Elsevier
ISSN:	0301-472X
Date of Acceptance:	15 April 2004
Last Modified:	26 Feb 2024 15:45
URI:	https://orca.cardiff.ac.uk/id/eprint/166064

Actions (repository staff only)

Edit Item