Original Research Article The expression pattern of APC2 and APC7 in various cancer cell lines and AML patients Hamzeh Rahimi a , Ahmad Ahmadzadeh b , Shamseddin Yousef-amoli a , Leila Kokabee a , Mohammad-Ali Shokrgozar c , Reza Mahdian a, *, Mortaza Karimipoor a, ** a Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran b Thalassemia and Hemoglobinopathy Research Center, Shafa Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran c National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran 1. Introduction Cancer is often caused by imbalanced cell proliferation and cell death, the two important aspects of ‘‘cell cycle’’ regulation. The ubiquitination pathway plays a critical role in cell cycle control and cell maintenance [1]. Two checkpoints have been discovered in the cell cycle regulation until now: anaphase promoting complex (APC/C) and SKP1-CUL1-F-boxprotein (SCF) [2]. The APC/C activa- tion occurs from the anaphase to the end of the G1 phase [3], while the SCF controls other steps of the cell cycle [4]. The APC/C, 1700-kDa protein complex, is the largest E3 ligase enzyme in human cells. The complex contains more than 13 subunits in three sub-complexes (catalytic, TPR, and scaffold complex) [5]. The catalytic subcomplex includes APC2, APC10/ Doc1 and APC11 subunits [6,7]. The tetratrico-peptide repeat (TPR) subcomplex contains APC3, APC6, APC7, and APC8 subunits [8,9]. These subunits play an important role in complex assembly and acceleration the interaction between catalytic subunits and its substrates [10,11]. The scaffold subcomplex is comprised of the largest subunits APC1, APC4 and APC5 [12]. The APC/C complex is activated by binding of a co-activator (Cdh1 and Cdc20) and phosphorylation of APC/C subunits [13,14]. The APC/C functions are divided into two groups: cell- cycle dependant and non-mitotic functions [15]. The APC/C also correlates the cell cycle with other pathways in cells, such as chromosome segregation [16], transcription machinery [17], DNA replication [18], TGF-beta signaling [19], and glycolysis [20]. This correlation guarantees that the cell growth and division occur at appropriate time. The APC/C complex performs its functions by Advances in Medical Sciences 60 (2015) 259–263 A R T I C L E I N F O Article history: Received 11 March 2014 Accepted 30 April 2015 Available online 13 May 2015 Keywords: Anaphase promoting complex Cell cycle Real-time PCR AML A B S T R A C T Purpose: Anaphase promoting complex (APC/C) is an E3 ligase enzyme, which ubiquinates various proteins involved in the cell cycle. This protein complex may have a pivotal role in the cell cycle control affecting pathological conditions such as cancer. APC7 and APC2 subunits of the APC/C complex are involved in the substrate recognition and the catalytic reaction, respectively. Materials and methods: In this study, quantitative Real-time PCR was used to analyse APC2 and APC7 expression in different cancer cell lines as well as AML patient’s blood cells. Results: The results showed that APC2 and APC7 subunits were both over expressed in cancer cell lines (p = 0.008). The mean expression ratio of APC2 and APC7 in different cancer cells were 2.60 Æ 0.22 and 4.83 Æ 0.11, respectively. An increase in expression of APC2 and APC7 was seen among 12 out of 14 AML patients (85%). There was a significant positive correlation between APC2 upregulation and the detection of splenomegaly in the patients (r = 0.808, p = 0.001). Conclusion: This was the first study suggesting that APC/C upregulation may contribute to the pathogenesis of cancer and can be used as a molecular biomarker to predict the progression and the prognosis of AML. ß 2015 Medical University of Bialystok. Published by Elsevier Sp. z o.o. All rights reserved. * Corresponding author at: Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, 12 Farvardin, Tehran, Iran. Tel.: +98 9127988388; fax: +98 2166480780. ** Corresponding author at: Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, 12 Farvardin, Tehran, Iran. Tel.: +98 9122806133; fax: +98 2166480780. E-mail addresses: rezamahdian@yahoo.com (R. Mahdian), mortezakarimi@yahoo.com (M. Karimipoor). Contents lists available at ScienceDirect Advances in Medical Sciences jo u rn al ho m epag e: ww w.els evier.c o m/lo cat e/advm s http://dx.doi.org/10.1016/j.advms.2015.04.007 1896-1126/ß 2015 Medical University of Bialystok. Published by Elsevier Sp. z o.o. All rights reserved.