Cyclic AMP-Induced P53 Destabilization is Independent of CREB in Pre-B Acute Lymphoblastic Leukemia Cells

Overview

Journal Int J Mol Cell Med

Specialty Genetics

Date 2017 Mar 31

PMID 28357198

Citations 2

Authors

Rima Manafi Shabestari

Majid Safa

Mehdi Banan

Ahmad Kazemi

Affiliations

Soon will be listed here.

Abstract

Elevated cAMP levels in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells attenuate the doxorubicin-induced p53 accumulation and protect cells against apoptosis. cAMP responsive element binding protein (CREB) is a cAMP-stimulated transcription factor that regulates genes whose deregulated expression cooperate in oncogenesis. In the present study, we investigated the role of CREB on inhibitory effect of cAMP on apoptosis and p53 accumulation in BCP-ALL NALM-6 cells. To determine whether targeting CREB can modulate the effect of cAMP on doxorubicin-induced apoptosis, we knocked down CREB in NALM-6 cells using lentiviral CREB shRNA. Knocked down cells were treated with doxorubicin in the presence or absence of cAMP-elevating agents. p53 protein level and apoptosis were assessed by western blot analysis and flow cytometry, respectively. p53 protein expression was reduced in cells treated with combination of cAMP-elevating agents and doxorubicin in contrast to cells treated with doxorubicin alone even in CREB-knocked down cells. Apoptosis assay showed that the cAMP-elevating agents decreased doxorubicin-induced apoptosis in CREB-knocked down and control cells. Although, CREB plays a particularly important role in cAMP signaling pathway our data suggest that CREB does not mediate the inhibitory effect of cAMP on doxorubicin-induced apoptosis and p53 accumulation in BCP-ALL NALM-6 cells.

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References

Garcia-Bermejo L, Perez C, Vilaboa N, de Blas E, Aller P . cAMP increasing agents attenuate the generation of apoptosis by etoposide in promonocytic leukemia cells. J Cell Sci. 1998; 111 ( Pt 5):637-44. DOI: 10.1242/jcs.111.5.637. View

Sakamoto K, Frank D . CREB in the pathophysiology of cancer: implications for targeting transcription factors for cancer therapy. Clin Cancer Res. 2009; 15(8):2583-7. PMC: 2883446. DOI: 10.1158/1078-0432.CCR-08-1137. View

Safa M, Mousavizadeh K, Noori S, Pourfathollah A, Zand H . cAMP protects acute promyelocytic leukemia cells from arsenic trioxide-induced caspase-3 activation and apoptosis. Eur J Pharmacol. 2014; 736:115-23. DOI: 10.1016/j.ejphar.2014.04.040. View

Lui K, An J, Montalbano J, Shi J, Corcoran C, He Q . Negative regulation of p53 by Ras superfamily protein RBEL1A. J Cell Sci. 2013; 126(Pt 11):2436-45. PMC: 3679486. DOI: 10.1242/jcs.118117. View

Gausdal G, Wergeland A, Skavland J, Nguyen E, Pendino F, Rouhee N . Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis. Cell Death Dis. 2013; 4:e516. PMC: 3734820. DOI: 10.1038/cddis.2013.39. View

Geier A, Weiss C, Beery R, Haimsohn M, Hemi R, Malik Z . Multiple pathways are involved in protection of MCF-7 cells against death due to protein synthesis inhibition. J Cell Physiol. 1995; 163(3):570-6. DOI: 10.1002/jcp.1041630318. View

Lomo J, Blomhoff H, Beiske K, Stokke T, Smeland E . TGF-beta 1 and cyclic AMP promote apoptosis in resting human B lymphocytes. J Immunol. 1995; 154(4):1634-43. View

Naderi E, Skah S, Ugland H, Myklebost O, Sandnes D, Torgersen M . Bone marrow stroma-derived PGE2 protects BCP-ALL cells from DNA damage-induced p53 accumulation and cell death. Mol Cancer. 2015; 14:14. PMC: 4323193. DOI: 10.1186/s12943-014-0278-9. View

Delghandi M, Johannessen M, Moens U . The cAMP signalling pathway activates CREB through PKA, p38 and MSK1 in NIH 3T3 cells. Cell Signal. 2005; 17(11):1343-51. DOI: 10.1016/j.cellsig.2005.02.003. View

10.

Pigazzi M, Ricotti E, Germano G, Faggian D, Arico M, Basso G . cAMP response element binding protein (CREB) overexpression CREB has been described as critical for leukemia progression. Haematologica. 2007; 92(10):1435-7. DOI: 10.3324/haematol.11122. View

11.

Banan M, Esmaeilzadeh-Gharehdaghi E, Nezami M, Deilami Z, Farashi S, Philipsen S . cAMP response element-binding protein 1 is required for hydroxyurea-mediated induction of γ-globin expression in K562 cells. Clin Exp Pharmacol Physiol. 2012; 39(6):510-7. DOI: 10.1111/j.1440-1681.2012.05702.x. View

12.

Safa M, Kazemi A, Zaker F, Razmkhah F . Cyclic AMP-induced p53 destabilization is independent of EPAC in pre-B acute lymphoblastic leukemia cells in vitro. J Recept Signal Transduct Res. 2011; 31(3):256-63. DOI: 10.3109/10799893.2011.578140. View

13.

Safa M, Kazemi A, Zand H, Azarkeivan A, Zaker F, Hayat P . Inhibitory role of cAMP on doxorubicin-induced apoptosis in pre-B ALL cells through dephosphorylation of p53 serine residues. Apoptosis. 2009; 15(2):196-203. DOI: 10.1007/s10495-009-0417-8. View

14.

Safa M, Tavasoli B, Manafi R, Kiani F, Kashiri M, Ebrahimi S . Indole-3-carbinol suppresses NF-κB activity and stimulates the p53 pathway in pre-B acute lymphoblastic leukemia cells. Tumour Biol. 2015; 36(5):3919-30. DOI: 10.1007/s13277-014-3035-1. View

15.

von Knethen A, Brune B . Attenuation of macrophage apoptosis by the cAMP-signaling system. Mol Cell Biochem. 2000; 212(1-2):35-43. View

16.

Naderi E, Findley H, Ruud E, Blomhoff H, Naderi S . Activation of cAMP signaling inhibits DNA damage-induced apoptosis in BCP-ALL cells through abrogation of p53 accumulation. Blood. 2009; 114(3):608-18. DOI: 10.1182/blood-2009-02-204883. View

17.

Naderi E, Jochemsen A, Blomhoff H, Naderi S . Activation of cAMP signaling interferes with stress-induced p53 accumulation in ALL-derived cells by promoting the interaction between p53 and HDM2. Neoplasia. 2011; 13(7):653-63. PMC: 3132851. DOI: 10.1593/neo.11542. View

18.

Insel P, Ostrom R . Forskolin as a tool for examining adenylyl cyclase expression, regulation, and G protein signaling. Cell Mol Neurobiol. 2003; 23(3):305-14. PMC: 11530207. DOI: 10.1023/a:1023684503883. View

19.

Yang P, Du C, Kwan M, Liang S, Zhang G . The impact of p53 in predicting clinical outcome of breast cancer patients with visceral metastasis. Sci Rep. 2013; 3:2246. PMC: 3718193. DOI: 10.1038/srep02246. View

20.

Vassilev L, Vu B, Graves B, Carvajal D, Podlaski F, Filipovic Z . In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004; 303(5659):844-8. DOI: 10.1126/science.1092472. View