Expression of chromosomal regional maintenance protein-1 may be associated with subcellular survivin expression in human gastric and colorectal carcinoma

Shintani, Michiko; Tashiro, Akito; Sangawa, Akiko; Yamao, Naoki; Kamoshida, Shingo

doi:10.3892/ol.2016.5220

Cited by 3 publications

(3 citation statements)

References 33 publications

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“…In this study we identified a high tendency of XPO1 overexpression towards the moderate/poorly differentiated tumors as well as increase of XPO1 overexpression frequency in advance tumor stages III-IV with significant difference. Although Shintani et al, (2016) studied the XPO1 expression in CRC tissue samples, they did not find such association in CRC tissues which may attribute to the large differences in the sample sizes in each of well and poorly differentiated tumor groups; others were found such association in other types of cancers such as ovarian cancer (Noske et al, 2008), glioma (Shen et al, 2009) and the XPO1 expression was increased from well to poorly differentiated breast tumors (Yue et al, 2018). Additionally, we noted that the poorly differentiated tumors were significantly increased numbers of metastatic lymph nodes, which goes in line with a cohort study results of 124,180 CRC patients by Ricciardi et al, (2006) who concluded that the poorly differentiated tumors were much more likely to be with lymph node positive than well-differentiated tumors.…”

Section: Discussionmentioning

confidence: 99%

Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer

Al-Adhraei

Al‐Thobhani

Poungvarin

et al. 2019

Asian Pac J Cancer Prev

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also known as chromosome region maintenance 1 (CRM1) protein, is involved in the homeostatic of nucleocytoplasmic transport of over 200 known cargos, most of them are tumor suppressor and cell cycle regulatory proteins such as p53, pRb, FOXOs, BRCA1/2 and inhibitor of NF-κB (Kau et al., 2004; Abstract Objectives: Exportin 1(XPO1), a nuclear exporter protein, has been gaining recognition in cancer progression and treatment. This study aimed to evaluate the association between the overexpression of XPO1 with NF-κB, Ki67 and clinicopathological characteristics in colorectal cancer (CRC) tissue samples and to explore the anti-proliferative effect of KPT-330, as XPO1 inhibitor, in colorectal cancer cell line. Methods: Forty CRC tissue samples were analyzed by immunostaining for the expressions of XPO1, NF-κB and Ki67 and then the anti-proliferative effect of the KPT-330 was also evaluated in HT29 colorectal cancer cell line. Results: XPO1 overexpression was observed in 52.5% of CRC and significantly apparent with strong intensity in tumor cells compared to the normal adjacent epithelium (P<0.001).Regarding to the histopathological characteristics, the XPO1 overexpression significantly associated with advanced tumor stages (P=0.049) and has great tendency towards moderate/poorly differentiated tumors. Although the XPO1 overexpression was strongly associated with high Ki67 expression (P=0.001), only Ki67 expression showed significant association with tumor size (P=0.012). No significant association was detected between the XPO1 overexpression and NF-κB, while the NF-κB positive expression was significantly associated with lymph node metastasis and Ki67 expression at P=0.027 and P= 0.007, respectively. The in vitro experiments showed a great impact of KPT-330, as XPO1 inhibitor, to inhibit cancer growth in dose and time dependent manner and significantly diminished the colony formation (P<0.001) of HT29 cells-associated with the expression of Ki67 (P<0.001). Conclusion: XPO1 overexpression and NF-κB expression may serve as potential biomarker associated with CRC pathogenesis and proliferation, while the KPT-330 is effectively inhibited-colon cancer growth in vitro. Further studies considering the prognostication role of XPO1 overexpression in CRC are required.

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Section: Discussionmentioning

confidence: 99%

Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer

Al-Adhraei

Al‐Thobhani

Poungvarin

et al. 2019

Asian Pac J Cancer Prev

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“…The XPO1, also known as chromosomal maintenance 1 (CRM1), is a nuclear export chaperone, mediates the nuclear export of several proteins which are essential for growth regulation and tumor suppression such as p53, leading to cytoplasmic degradation (9). Overexpression of XPO1 is identified in CRC (10) and the accumulated evidence suggests that both p53 and XPO1 are working in reciprocal manner, while the XPO1 gene has a binding site for p53 and its transcription activity may be repressed by p53, the increased activity of XPO1 can cause the p53 mislocalization and dysfunction in cancers (11,12). From the above indications and because of individual marker expression has a limited prognostic value, we aimed to evaluate the association between the expression of p53 and clinicopathological features in CRC Yemeni patents, which is still unknown, and tried to explore the ambiguous relationship between the coexpression of p53 and XPO1 in CRC tissue samples in relation to histopathological features.…”

Section: Introductionmentioning

confidence: 99%

The roles of p53 and XPO1 on colorectal cancer progression in Yemeni patients

Al-Adhraei

Al-Salami

Poungvarin

et al. 2019

J. Gastrointest. Oncol

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Background: The colorectal cancer (CRC) tumorigenesis is driving by genetic alterations leading to changes in protein expression such as p53. The p53 is frequently expressed in CRC and its association with clinicopathological features is still controversial. Moreover, accumulated evidence suggests that both p53 and nuclear exporter protein, exportin 1 (XPO1), are working in reciprocal manner may lead to loss of p53 nuclear localization and enhance cancer progression through hyperactive nuclear export. Accordingly, the present study aimed to evaluate the expression of p53 in CRC Yemeni patients and to explore the association between the p53 and XPO1 coexpression in relation to clinicopathological features. Methods: A series of 40 formalin fixed paraffin embedded (FFPE) tissue blocks taken from CRC patients that diagnosed as adenocarcinoma were prospectively collected and then analyzed for p53 and XPO1 expression by immunohistochemistry (IHC). The patients and tumor clinicopathological characteristics were retrieved from the histopathology reports and the P value <0.05 were considered statistically significant. Results: The p53 expression was observed in 60% (24/40) of CRC tumor samples. Significantly, the p53 expression was noted in 72.4% (21/29) of the left side compared to 27.3% (3/11) of the right side colon tumors (P=0.014). Furthermore, p53 expression was positively and significantly correlated with well-but not moderate-or poorly-differentiated tumors (P=0.023). No significant difference was observed between the p53 expression and age, gender and tumor size. Regarding the XPO1 expression, the p53 expression didn't show an association with XPO1 expression. The coexpression of p53 and XPO1 analysis revealed that 100% (11/11) tumors with negative p53 and positive XPO1 coexpression was noted with lymph node metastasis with significant difference (P=0.003) and more frequently observed in moderate-or poorly-differentiated tumors. Conclusions: The loss of p53 accompanied with increased XPO1 expressions was associated with the progression of histopathological features of CRC Yemeni patients. Further studies are needed to elucidate the p53 genetic mutations in relation to the XPO1 coexpression in CRC prognosis.

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“…The survivin protein inhibits caspase activation, thereby leading to negative regulation of apoptosis. This has been demonstrated by the disruption of survivin induction pathways leading to an increase in apoptosis and a decrease in tumor growth (50,51). Survivin inhibits both Bax and Fas-induced apoptotic pathways and blocks apoptosis by directly inhibiting caspases (52).…”

Section: Discussionmentioning

confidence: 99%

Anticancer effects of β-elemene with hyperthermia in lung cancer cells

Wang²,

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. β-elemene is a novel, plant-derived anticancer drug, which has been used to target multiple solid tumor types. Hyperthermia is an adjuvant therapeutic modality to treat cancer. However, the underlying mechanisms associated with the efficacy of these two treatments are largely unknown. The aim of the present study was to evaluate the effects of β-elemene combined with hyperthermia in lung cancer cell lines. An MTT assay was used to determine cell viability. The cell cycle and apoptosis were analyzed using flow cytometry. The morphology of cells during apoptosis was determined using a transmission electron microscope. The expression levels of P21, survivin, caspase-9, B-cell lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax) mRNA were detected using quantitative polymerase chain reaction. β-elemene with hyperthermia treatment significantly inhibited the viability and increased the apoptosis rate of A549 cells compared with β-elemene treatment alone (P<0.01), and significantly decreased the proportion of cells in S phase compared with the control (P<0.01). Morphological observation using transmission electron microscopy indicated cross-sectional features of apoptosis: Chromatin condensation, reduced integrity of the plasma membrane, increased cellular granularity, nuclear collapse and the formation of apoptotic bodies. β-elemene with hyperthermia treatment significantly promoted P21 and Bax mRNA expression (P<0.01) and significantly decreased caspase-9, Bcl-2 and survivin mRNA expression (P<0.01) in A549 cells. In conclusion, β-elemene with hyperthermia has a significant inhibitory effect on A549 cells. This occurs through reducing S phase and inducing apoptosis, via an increase in P21 and Bax expression and a decrease in caspase-9, Bcl-2 and survivin expression.

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Expression of chromosomal regional maintenance protein-1 may be associated with subcellular survivin expression in human gastric and colorectal carcinoma

Cited by 3 publications

References 33 publications

Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer

Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer

The roles of p53 and XPO1 on colorectal cancer progression in Yemeni patients

Anticancer effects of β-elemene with hyperthermia in lung cancer cells

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