Abstract
BackgroundMcl-1, an anti-apoptotic member of bcl-2 family, together with cleaved poly (ADC-ribose) polymerase (c-PARP) can serve as a marker of cell apoptosis. Previously we reported that treatment of Mnk inhibitor CGP57380 resulted in decreased Mcl-1 expression while increased c-PARP expression in non-small cell lung cancer (NSCLC) cells. In this study, we aimed to investigate association between Mcl-1 expression and clinicopathological features of NSCLC, and their correlation between Mcl-1 and both proliferation index (PI) and apoptotic index (AI) in NSCLC patients.MethodsTissue microarrays (TMA) including 350 cases of surgically resected NSCLC were utilize and stained with Mcl-1, Ki-67 and c-PARP antibodies, PI and AI were then evaluated, respectively.ResultsHigher Mcl-1 expression and PI were observed in NSCLC compared with non-cancerous lung tissues (non-CLT), while AI was significantly lower in lung adenocarcinoma (ADC) compared with non-CLT. Additionally, Mcl-1 expression in lung ADC was evidently higher than that of in lung squamous cell carcinoma (SCC). The elevated Mcl-1 expression was associated with PI, and inversely related to AI in NSCLC. NSCLC patients with elevated Mcl-1 expression and high PI, or with high Mcl-1 expression and low AI had remarkably shorter overall survival time than these patients with low Mcl-1 expression.ConclusionsElevated expression of Mcl-1 might be inversely proportional to disease progression of NSCLC patients by promoting cell proliferation and inhibiting apoptosis, and Mcl-1 might serve as novel biomarker of poor prognosis for NSCLC patients.
Highlights
Myeloid cell leukemia 1 (Mcl-1), an anti-apoptotic member of bcl-2 family, together with cleaved poly (ADC-ribose) polymerase (c-poly ADP-ribose polymerase (PARP)) can serve as a marker of cell apoptosis
We previously reported that treatment of Mnk inhibitor CGP57380 with Non-small cell lung cancer (NSCLC) cells results in different expression pattern of Mcl-1 and cleaved poly (ADC-ribose) polymerase (c-PARP), Mcl-1 expression is decreased whereas c-PARP is increased, the later plays an important role in inducing cell apoptosis through activating intrinsic mitochondrial pathway and represents cancer cell apoptotic index (AI)
Association between mcl-1 expression, proliferation index (PI) and AI and clinicopathological features of NSCLC Strong Mcl-1 expression (Fig. 1b and c) was found in cytoplasm of lung squamous cell carcinoma (SCC) and ADC cells while no Mcl-1 expression was detected in non-cancerous lung tissues (non-CLT) (Fig. 1a)
Summary
Mcl-1, an anti-apoptotic member of bcl-2 family, together with cleaved poly (ADC-ribose) polymerase (c-PARP) can serve as a marker of cell apoptosis. We reported that treatment of Mnk inhibitor CGP57380 resulted in decreased Mcl-1 expression while increased c-PARP expression in non-small cell lung cancer (NSCLC) cells. Non-small cell lung cancer (NSCLC), which includes squamous cell carcinoma (SCC) and adenocarcinoma (ADC), is the major histological subtypes and accounts for more than 80% of primary lung tumors [1]. Myeloid cell leukemia 1 (Mcl-1), an anti-apoptotic member of the B-cell lymphoma 2 (bcl-2) family of apoptosis-regulating proteins, exemplifies a number of the mechanisms by which a protein’s contribution to cell fate may be modified [3]. Overexpression of Mcl-1 induces oncogenic transformation, and increased expression of Mcl-1 protein is found in the majority of human cancer including NSCLC.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
