Expression of Mcl-1 and p53 proteins predicts the survival of patients with T3 gastric carcinoma

Maeta, Yoshihiko; Tsujitani, Shunichi; Matsumoto, Sachiko; Yamaguchi, Kensei; Tatebe, Shigeru; Kondo, Akira; Ikeguchi, Masahide; Kaibara, Nobuaki

doi:10.1007/s10120-004-0272-9

Cited by 27 publications

(36 citation statements)

References 21 publications

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“…The results demonstrated that: (1) Mcl-1-expressing gastric cancer cells were relatively resistant to chemotherapeutic agents such as 5-FU and CDDP; (2) suppression of Mcl-1 protein by shRNA technology successfully enhanced chemotherapy sensitivity; (3) Mcl-1 suppression also enhanced 5-FUmediated apoptosis-related events, including mitochondrial cytochrome c release and caspase-3 activation; and (4) chemotherapy resistance in the so-called CSC-like CD44-positive population was mediated by enhanced Mcl-1 expression. Our results are consistent with a previous report using antisense-based technology which has shown that Mcl-1 is a therapeutic target in gastric cancer cells [9]. In addition, our study is the first to demonstrate that Mcl-1 expression is relatively enhanced in CD44-positive gastric cancer cells.…”

Section: Discussionsupporting

confidence: 93%

“…We recently found that the best results for sensitization to chemotherapy by Mcl-1 suppression were obtained with gastric cancer. In support of our results, a recent report suggests that Mcl-1 expression is enhanced in gastric cancer and the expression level predicts the prognosis [9]. In addition, an antisense approach to inhibit Mcl-1 successfully enhanced sensitivity to chemotherapy drugs in gastric cancer cell lines [10].…”

Section: Introductionsupporting

confidence: 89%

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Suppression of myeloid cell leukemia-1 (Mcl-1) enhances chemotherapy-associated apoptosis in gastric cancer cells

et al. 2012

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Section: Discussionsupporting

confidence: 93%

Section: Introductionsupporting

confidence: 89%

Suppression of myeloid cell leukemia-1 (Mcl-1) enhances chemotherapy-associated apoptosis in gastric cancer cells

et al. 2012

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“…Downregulation of the Mcl-1 expression in A11 cells by Mcl-1 siRNA increased the sensitivity to hypoxia-induced cell death and, importantly, decreased the metastatic ability. Although there are so far few reports directly indicating the involvement of Mcl-1 in metastatic potential of tumor cells, a clinicopathological study suggested Mcl-1 as an indicator of tumor progression and prognosis in patients with gastric carcinoma (Maeta et al, 2004). Therefore, Mcl-1 may be one of the factors that confer metastatic potential on at least some tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia selects for high-metastatic Lewis lung carcinoma cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors

et al. 2005

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Low oxygen tension (hypoxia) is a common feature of solid tumors and stimulates the expressions of a variety of genes including those related to angiogenesis, apoptosis and endoplasmic reticulum (ER) stress response. Here we show a close correlation between metastatic potential and the resistance to hypoxia-and ER stress-induced apoptosis among the cell lines with differing metastatic potential derived from Lewis lung carcinoma. An apoptosis-specific expression profiling and immunoblot analyses revealed that the expression of antiapoptotic Mcl-1 increased as the resistance to apoptosis increased. Downregulation of the Mcl-1 expression in the high-metastatic cells by Mcl-1 small interfering RNA increased the sensitivity to hypoxia-induced apoptosis and decreased the metastatic ability. The hypoxia-induced apoptosis was not associated with p53 accumulation, although at present it is not possible to conclude that apoptosis-induced apoptosis is p53-independent. There was no correlation between the expression levels of ER stress-response proteins GADD153, GRP78 and ORP150 and the resistance to hypoxia or ER stresses. In vitro, small numbers of the high-metastatic cells overtook the low-metastatic cells after exposure to several rounds of hypoxia and reoxygenation. In solid tumors initially established from equal mixtures, the proportion of the high-metastatic cells to low-metastatic cells was significantly higher in hypoxic areas. Moreover, the high-metastatic cells were overtaking the low-metastatic cells in some of the tumors. Thus, tumor hypoxia and ER stress may provide a physiological selective pressure for the expansion of the high-metastatic cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors.

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“…The biological relevance of Mcl-1 as an anti-apoptotic protein promoting cell survival has been reported in various human malignancies (Zhou et al, 1997;Shigemasa et al, 2002;Taniai et al, 2004). Elevated expression of Mcl-1 and its association with poor prognosis have been reported in gastric cancer (Krajewska et al, 1996;Maeta et al, 2004). Interestingly, Wacheck et al (2006) have proposed Mcl-1 antisense therapy as a promising approach for the treatment of gastric cancer.…”

Section: Epigenetic Activation Of Mir-512-5p Y Saito Et Almentioning

confidence: 99%

Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells

et al. 2009

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Epigenetic therapy using DNA methylation inhibitors and histone deacetylase (HDAC) inhibitors has clinical promise for the treatment of human malignancies. To investigate roles of microRNAs (miRNAs) on epigenetic therapy of gastric cancer, the miRNA expression profile was analysed in human gastric cancer cells treated with 5-aza-2 0 -deoxycytidine (5-Aza-CdR) and 4-phenylbutyric acid (PBA). miRNA microarray analysis shows that most of miRNAs activated by 5-Aza-CdR and PBA in gastric cancer cells are located at Alu repeats on chromosome 19. Analyses of chromatin modification show that DNA demethylation and HDAC inhibition at Alu repeats activates silenced miR-512-5p by RNA polymerase II. In addition, activation of miR-512-5p by epigenetic treatment induces suppression of Mcl-1, resulting in apoptosis of gastric cancer cells. These results suggest that chromatin remodeling at Alu repeats plays critical roles in the regulation of miRNA expression and that epigenetic activation of silenced Alu-associated miRNAs could be a novel therapeutic approach for gastric cancer.

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Expression of Mcl-1 and p53 proteins predicts the survival of patients with T3 gastric carcinoma

Cited by 27 publications

References 21 publications

Suppression of myeloid cell leukemia-1 (Mcl-1) enhances chemotherapy-associated apoptosis in gastric cancer cells

Suppression of myeloid cell leukemia-1 (Mcl-1) enhances chemotherapy-associated apoptosis in gastric cancer cells

Hypoxia selects for high-metastatic Lewis lung carcinoma cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors

Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells

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