Poly(ADP-ribose) polymerase (PARP) is an enzyme that mediates post-translational modification of proteins. Seventeen known members of the PARP superfamily can be grouped into three classes based on catalytic activity: (i) classical poly(ADP-ribose) polymerases, (ii) mono(ADP‑ribosyl) transferases and (iii) catalytically inactive members. PARP6 belongs to the mono(ADP-ribosyl) transferase class, and here we have found that PARP6 is a negative regulator of cell proliferation. Forced expression of PARP6 in HeLa cells induced growth suppression, but a PARP6 mutant with a C-terminal deletion lacking the catalytic domain had no effect. The PARP6-expressing cells accumulated in the S-phase, and the magnitude of S-phase accumulation was observed to be greater in cells expressing a PARP6 mutant with an N-terminal deletion, lacking a putative regulatory domain. Immunohistochemical analysis revealed that PARP6 positivity was found at higher frequencies in colorectal cancer tissues with well-differentiated histology compared to those with poorly differentiated histology. Furthermore, PARP6 positivity negatively correlated with the Ki-67 proliferation index. Kaplan-Meier analysis showed that PARP6-positive colorectal cancer had a good prognosis. Based on these results, we propose that PARP6 acts as a tumor suppressor through its role in cell cycle control.
The ever increasing use of cellular phones and the increasing number of associated base stations are becoming a widespread source of nonionizing electromagnetic radiation. Some biological effects are likely to occur even at low-level EM fields. In this study, a gigahertz transverse electromagnetic (GTEM) cell was used as an exposure environment for plane wave conditions of far-field free space EM field propagation at the GSM base transceiver station (BTS) frequency of 945 MHz, and effects on oxidative stress in rats were investigated. When EM fields at a power density of 3.67 W/m2 (specific absorption rate = 11.3 mW/kg), which is well below current exposure limits, were applied, MDA (malondialdehyde) level was found to increase and GSH (reduced glutathione) concentration was found to decrease significantly (p < 0.0001). Additionally, there was a less significant (p = 0.0190) increase in SOD (superoxide dismutase) activity under EM exposure.
These results suggest that molecular mechanisms of genomic instability are not necessarily independent and may not be fully defined by either the MSI or CIN pathways in sporadic gastric cancers.
Abstract. The chromosomal passenger complex (CPC) is a key regulator of chromosome segregation and cytokinesis, and consists of Aurora B kinase, INCENP, Survivin and Borealin. Aurora B is a member of a family of serine/threonine protein kinases, and Survivin belongs to the inhibitors of apoptosis (IAP) gene family, and is also a member of the CPC family. Aurora B and Survivin have also been reported to be overexpressed in various human cancers; however, as yet no studies have investigated the co-expression of Survivin and Aurora B in colorectal carcinoma. Therefore, in the present study, the correlation between Aurora B and Survivin expression was investigated using immunohistochemistry and the associated pathological features in colorectal carcinoma were analyzed. Our present findings showed that nuclear Aurora B and cytoplasmic Survivin expression are strongly associated with and involved in lymph node metastasis in colorectal cancer. Therefore, we suggest that nuclear Aurora B and cytoplasmic Survivin are useful diagnostic markers and therapeutic targets in colorectal carcinoma.
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