International Journal of Molecular and Cellular Medicine
مجله بین المللی سلولی و مولکولی
Int J Mol Cell Med
Medical Sciences
http://ijmcmed.org
1
admin
2251-9637
2251-9645
10.22088/IJMCM.BUMS
en
jalali
1395
8
1
gregorian
2016
11
1
5
4
online
1
fulltext
en
Cyclic AMP-induced p53 Destabilization is Independent of CREB in pre-B Acute Lymphoblastic Leukemia Cells
Cancer
Cancer
Original Article
Original Article
<p style="text-align: justify;">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.</p>
Apoptosis, cAMP, CREB, doxorubicin, p53
220
228
http://ijmcmed.org/browse.php?a_code=A-10-987-1&slc_lang=en&sid=1
Rima
Manafi Shabestari
manafirima@gmail.com
10031947532846008691
10031947532846008691
No
Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
Majid
Safa
majidsafa@gmail.com
10031947532846008692
10031947532846008692
Yes
Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
Mehdi
Banan
mbbanan@yahoo.com
10031947532846008693
10031947532846008693
No
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Ahmad
Kazemi
aKazemi32@gmail.com
10031947532846008694
10031947532846008694
No
Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.