Survivin Gene Expression Positively Correlates with Proliferative Activity of Cancer Cells in Esophageal Cancer

Tumor Biology ◽  
2003 ◽  
Vol 24 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Masahide Ikeguchi ◽  
Ken-ichi Yamaguchi ◽  
Nobuaki Kaibara
Keyword(s):  
Gene Expression ◽  
Esophageal Cancer ◽  
Cancer Cells ◽  
Proliferative Activity ◽  
Survivin Gene

HIF-1 Supports the Survival of Multiple Myeloma Cells through the Induction of Survivin Gene.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 110-110 ◽  
Author(s):  
Keita Kirito ◽  
Hu Yongzhen ◽  
Kozue Yoshida ◽  
Toru Mitsumori ◽  
Kei Nakajima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Cancer Cells ◽  
Cell Lines ◽  
Dependent Manner ◽  
Survivin Mrna ◽  
Myeloma Cells ◽  
Survivin Gene ◽  
Growth And Survival ◽  
Induced Apoptosis

Abstract In spite of the recent development of therapeutic strategies, multiple myeloma (MM) still remains incurable. Several cytokines and chemokines contribute to progression of the disease and acquisition of resistance to chemotherapy. These humoral factors support the growth and survival of myeloma cells through the regulation of transcription factors including NF-κB, Stat3 and FOXO3a. Hypoxia inducible factor-1 (HIF-1) is an important transcription factor that is activated under low oxygen tension and controls dozens of genes involved in angiogenesis, energy production and resistance to apoptosis. Interestingly, HIF-1 is frequently activated in cancer cells even under normoxic condition and it is well established that HIF-1 expression and activation correlates with tumor progression and resistance to cancer treatments. In this study, we investigated whether HIF-1 is involved in the biology of multiple myeloma. To this end, we used three MM cell lines U266, RPMI8226 and KMM-1. After informed consent, we also prepared primary MM cells from bone marrow samples of patients (n=5) using anti-CD138 magnetic beads. Initially, we treated MM cells with insulin-like growth factor-1 (IGF-1) and IL-6, both of which are major growth and survival factors for myeloma cells. Treatment with IGF-1 and, to be a lesser degree, IL-6 clearly enhanced expression of HIF-1α, a subunit of HIF-1, in all three cell lines. Similar results were obtained from isolated primary MM cells. Based on several lines of evidence that survivin, a member of inhibitor of apoptosis (IAP) family protein, is transcriptionally regulated by HIF-1 in breast cancer cells, and that this anti-apoptotic factor is important for growth of MM cells, we examined whether HIF-1 supports the survival of MM cells through the induction of survivin. Quantitative RT-PCR assay revealed that IGF-1 increased survivin mRNA both in MM cell lines and in primary MM cells. In addition, IGF-1 activated survivin gene promoter containing a HIF-1-binding site. To confirm that IGF-1-induced activation of survivin gene is mediated by HIF-1, we treated MM cell lines with echinomycin, an inhibitor of DNA-binding activity of HIF-1. As expected, echinomycin inhibited IGF-1-induced survivin gene expression in a dose-dependent manner. The inhibitor also induced apoptosis of MM cells, and IGF-1 could not rescue the MM cells from echinomycin-induced apoptosis. Furthermore, echinomycin enhanced melphalan-induced apoptosis of MM cells. To further examine the involvement of HIF-1 in IGF-1-induced survivin gene expression, we generated three independent HIF-1α knockdown KMM-1 clones using siRNA system. Survivin mRNA was not detected in the HIF-1α knockdown cells, and these clones easily underwent apoptosis even in the presence of IGF-1, compared to the parental cells. Taken together, HIF-1 plays a pivotal role in survival of MM cells through the induction of survivin gene. In conclusion, HIF-1 might be an attractive therapeutic target for MM.

Oncolytic adenovirus expressing apoptotic genes targets radiation resistant (RR) esophageal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21043-21043
Author(s):  
J. Y. Chang ◽  
R. Komaki ◽  
X. Zhang ◽  
L. Wang ◽  
B. Fang
Keyword(s):  
Gene Expression ◽  
Esophageal Cancer ◽  
Radiation Exposure ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Esophageal Cancer Cell ◽  
Esophageal Cancer Cells ◽  
Trans Gene ◽  
Fractionated Radiation

21043 Background: Only 25% of esophageal cancer patients achieve pathological complete response after standard chemoradiotherapy. Radiation dose escalation is associated with higher toxicity but no therapeutic improvement. In addition, esophageal cancer cells may develop radiation resistance (RR) after fractionated radiation exposure. Therefore, molecular targeting therapy for RR esophageal cancer is urgently needed. Methods: Six pairs of RR esophageal cancer cell lines were established by applying continuous 2 Gy fractionated irradiation. Ad/TRAIL-E1, an oncolytic adenoviral vector expressing both apoptotic TRAIL and viral E1A genes under the control of tumor specific human telomerase reverse transcriptase promoter, was constructed. Phosphate buffer solution and vectors expressing the TRAIL gene only, the GFP marker protein only, or the E1A gene only served as controls. Trans-gene expression, apoptosis activation, and the RR esophageal cancer cells targeted were evaluated in vitro and in vivo. A human esophageal RR cancer model was established and locally treated with Ad/TRAIL-E1 or controls. Results: After fractionated radiation exposure, esophageal cancer cell lines developed RR (up to 25-fold) that was associated with activation of the anti-apoptotic pathway. Ad/TRAIL-E1 activated an apoptotic cascade of caspases and selectively killed esophageal cancer cells but not normal cells. Ad/TRAIL-E1 preferentially targeted RR stem-like cancer cells with higher trans-gene expression and cell killing compared with parental cells. Overexpression (3 times) of Coxsackie's and adenoviral receptors in RR esophageal cancer cells compared with parental cells was noted. Ad/TRAIL-E1 therapy resulted in 40% tumor-free survival without the treatment- related toxicity found in human RR esophageal adenocarcinoma mouse models (p<0.05 as compared with controls). Conclusions: Esophageal cancer cells develop RR after fractionated radiation exposure. Ad/TRAIL-E1 preferentially targeted RR stem-like esophageal cancer cells, which resulted in a 40% cure rate. No significant financial relationships to disclose.

M1753 Survivin Gene Expression in Blood As a Prognostic Marker in the Surgical Therapy of Patients with Esophageal Cancer

2009 ◽  
Vol 136 (5) ◽  
pp. A-905
Author(s):  
Daniel Vallbohmer ◽  
Andreas C. Hoffmann ◽  
Peter Grimminger ◽  
Frederike C. Ling ◽  
Ralf Metzger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Esophageal Cancer ◽  
Prognostic Marker ◽  
Surgical Therapy ◽  
Survivin Gene

scholarly journals Evaluation of the effect of amygdalin on survivin gene expression in MCF-7 breast cancer cell line

Genetika ◽  
2018 ◽  
Vol 50 (2) ◽  
pp. 647-657
Author(s):  
Iman Shahrokhiyan ◽  
Abbas Doosti ◽  
Hossein Sazegar
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Cell Lines ◽  
Mtt Assay ◽  
Breast Cancer Cells ◽  
Rt Pcr ◽  
Survivin Gene ◽  
Cell Groups ◽  
Mcf 7

The effects of amygdalin as an herbal substance on prevention of cancer cells proliferation it has been shown. Also, survivin gene is one of the important genes on inhibition of apoptosis and controlling of the cell cycle in cancer cell lines. For this purpose, the present study was undertaken for the first time to evaluate the effects of amygdalin on survivin gene expression in MCF-7 and HDF. The MCF-7 (Breast cancer cells) and normal HDF were treated by different doses of amygdalin (0.5 to 10 mg/ml). Then, the MTT assay was done on each cell groups on 24, 48, and 72 h after treatment. In each period time the cells were detached and used for RNA extraction and cDNA synthesis. Finally, the survivin gene expression in each cell groups was evaluated by quantitative real-time PCR (q-RT-PCR) analysis. The MTT assay was showed that 5 mg/ml of amygdalin concentration at 48 hours after treatment it was suitable for evaluation of this compound on MCF-7 and HDF cell lines. The survey results of q-RT-PCR were showed in both amygdalin-treated MCF-7 (MCF-7+AMG) compare to the treated HDF (HDF-AMG as an control group) the expression level of survivin gene were decreased but this reduction only in MCF-7+AMG group was statistically significant (p <0.05). Our findings indicated that amygdalin in particular; decrease the survivin mRNA in MCF-7 breast cancer cells compare to normal healthy cells and leads to apoptosis and the death of cancer cells. It is suggested that in future study it must be better the effects of amygdalin supplemented with surfactant investigate against other cancer cells and evaluate the more molecular markers to specify the anti-cancer activity potential of this herbal compound.

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