In the erythroleukemic cell line HEL Prostate-apoptosis-response-gene-4 (par-4) fails to down-regulate Bcl-2 and to promote apoptosis.

Boehrer, Simone, Brieger, Angela, Schaaf, Simone, Kukoc-Zivojnov, Natasa, Nowak, Daniel, Ruthardt, Martin ORCID: https://orcid.org/0000-0003-1021-3811, Hoelzer, Dieter, Mitrou, Paris S, Weidmann, Eckhart and Chow, Kai Uwe 2004. In the erythroleukemic cell line HEL Prostate-apoptosis-response-gene-4 (par-4) fails to down-regulate Bcl-2 and to promote apoptosis. Leukemia & Lymphoma 45 (7) , pp. 1445-1451. 10.1080/10428190410001663617

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Abstract

In a variety of malignant cells Prostate-apoptosis-response-gene-4 (Par-4) exhibits a pro-apoptotic influence sensitizing these cells to apoptosis-inducing agents by downregulating expression of Bcl-2. Considering the crucial role of Bcl-2 in the development of chemoresistance of acute myeloid leukemia (AML) cells, we here assessed the potential of Par-4 to down-regulate Bcl-2 and to induce apoptosis in the erythroleukemic cell line HEL. Testing a potential pro-apoptotic role of Par-4 upon incubation with various conventional chemotherapeutic drugs, novel agents such as the signal transduction inhibitor STI 571 and the histone deacetylase (HDAC)- inhibitor trichostatin A (TSA), as well as with the experimental substances Fas and TRAIL, we provide evidence that in the erythroleukemic cell line HEL expression of Par-4 is not sufficient to sensitize to any of these pro-apoptotic stimuli. We further demonstrate that--in contrast to previous reports in non-AML cells--Par-4 expression in HEL cells leads to an upregulation of Bcl-2. Moreover, Par-4-positive HEL cells exhibit a decreased level of the proapoptotic protein Bax as compared to Par-4- negative cells. In addition, Par-4 increases the expression of Daxx--whose downregulation is associated with augmented chemosensitivity--as well as expression of the procaspases-8, -9 and -10, whereas the levels of the procaspases-3 and -7 remain unaltered. In conclusion we here demonstrate that in the erythroleukemic cell line HEL--in contrast to other cell types Par-4 fails to promote apoptosis and outline the underlying molecular mechanisms.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Taylor and Francis Group
ISSN:	1042-8194
Date of Acceptance:	29 December 2003
Last Modified:	26 Feb 2024 16:16
URI:	https://orca.cardiff.ac.uk/id/eprint/166062

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