:: Volume 5, Number 4 (Int J Mol Cell Med 2016) ::
Int J Mol Cell Med 2016, 5(4): 220-228 Back to browse issues page
Cyclic AMP-induced p53 Destabilization is Independent of CREB in pre-B Acute Lymphoblastic Leukemia Cells
Rima Manafi Shabestari1, Majid Safa *2, Mehdi Banan3, Ahmad Kazemi1
1- Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran., Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
2- Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran., Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. , majidsafa@gmail.com
3- Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Abstract:   (1157 Views)

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 cooperatein oncogenesis. In the present study, we investigated the role of CREB on inhibitory effect of cAMP on apoptosis and p53 accumulation in BCP-ALLNALM-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. CREB plays a particularly important role in cAMP signaling pathway. However, 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.

Keywords: Apoptosis, cAMP, CREB, doxorubicin, p53
Full-Text [PDF 350 kb]   (419 Downloads)    
Type of Study: Original Article | Subject: Cancer
Received: 2016/10/21 | Accepted: 2016/12/31 | Published: 2017/01/14



DOI: 10.22088/acadpub.BUMS.5.4.220


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Volume 5, Number 4 (Int J Mol Cell Med 2016) Back to browse issues page