• Journal of Life Science
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• v.23 no.10
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• pp.1230-1238
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• 2013

The regulatory effect of the tumor-suppressor protein p53 on the apoptogenic activity of $17{\alpha}$-estradiol ($17{\alpha}-E_2$) was compared between HCT116 ($p53^{+/+}$) and HCT116 ($p53^{-/-}$) cells. When the HCT116 ($p53^{+/+}$) and HCT116 ($p53^{-/-}$) cells were treated with $2.5{\sim}10{\mu}M$ $17{\alpha}-E_2$ for 48 h or with $10{\mu}M$for various time periods, cytotoxicity and an apoptotic sub-$G_1$ peak were induced in the HCT116 ($p53^{+/+}$) cells in a dose- and time-dependent manner. However, the HCT116 ($p53^{-/-}$) cells were much less sensitive to the apoptotic effect of $17{\alpha}-E_2$. Although $17{\alpha}-E_2$ induced aberrant mitotic spindle organization and incomplete chromosome congregation at the equatorial plate, $G_2/M$ arrest was induced to a similar extent in both cell types. In addition, $17{\alpha}-E_2$-induced activation of Bak and Bax, ${\Delta}{\Psi}m$ loss, and PARP degradation were more dominant in the HCT116 ($p53^{+/+}$) than in the HCT116 ($p53^{-/-}$) cells. In accordance with enhancement of p53 phosphorylation (Ser-15) and p53 levels, p21 and Bax levels were elevated in the HCT116 ($p53^{+/+}$) cells treated with $17{\alpha}-E_2$. The HCT116 ($p53^{-/-}$) cells exhibited barely or undetectable levels of p21 and Bax, regardless of $17{\alpha}-E_2$ treatment. On the other hand, although the level of Bcl-2 was slightly lower in the HCT116 ($p53^{+/+}$) than in the HCT116 ($p53^{-/-}$) cells, it remained relatively constant after the $17{\alpha}-E_2$ treatment. Together, these results show that among the components of the $17{\alpha}-E_2$-induced apoptotic-signaling pathway, which proceeds through mitotic spindle defects causing mitotic arrest, subsequent activation of Bak and Bax and the mitochondria-dependent caspase cascade, leading to PARP degradation, $17{\alpha}-E_2$-induced activation of Bak and Bax is the upstream target of proapoptotic action of p53.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.785-795
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• 1997

Background : Tumor markers have been used in diagnosis, predicting the extent of disease, monitoring recurrence after therapy and prediction of prognosis. But the utility of markers in lung cancer has been limited by low sensitivity and specificity. TPA-M is recently developed marker using combined monoclonal antibody of Cytokeratin 8, 18, and 19. This study was conducted to evaluate the efficacy of new tumor marker, TPA-M by comparing the estabilished markers SCC, CEA, Cyfra21-1 in lung cancer. Method : An immunoradiometric assay of serum CEA, sec, Cyfra21-1, and TPA-M was performed in 49 pathologically confirmed lung cancer patients who visited Keimyung University Hospital from April 1996 to August 1996, and 29 benign lung diseases. Commercially available kits, Ab bead CEA (Eiken) to CEA, SCC RIA BEAD (DAINABOT) to SCC, CA2H (TFB) to Cyfra2H. and TPA-M (DAIICHI) to TPA-M were used for this study. Results : The mean serum values of lung cancer group and control group were $10.05{\pm}38.39{\mu}/L$, $1.59{\pm}0.94{\mu}/L$ in CEA, $3.04{\pm}5.79{\mu}/L$, $1.58{\pm}2.85{\mu}/L$ in SCC, $8.27{\pm}11.96{\mu}/L$, $1.77{\pm}2.72{\mu}/L$ in Cyfra21-1, and $132.02{\pm}209.35\;U/L$, $45.86{\pm}75.86\;U/L$ in TPA-M respectively. Serum values of Cyfra21-1 and TPA-M in lung cancer group were higher than control group (p<0.05). Using cutoff value recommended by the manufactures, that is $2.5{\mu}/L$ in CEA, $3.0{\mu}/L$ in Cyfra21-1, 70.0 U/L in TPA-M, and $2.0{\mu}/L$ in SCC, sensitivity and specificity of lung cancer were 33.3%, 78.6% in CEA, 50.0%, 89.7% in Cyfra21-1, 52.3%, 89.7% in TPA-M, 23.8%, 89.3% in SCC. Sensitivity and specificity of nonsmall cell lung cancer were 36.1%, 78.1% in CEA, 50.1%, 89.7% in Cyfra21-1, 53.1%, 89.7% in TPA-M, 33.8%, 89.3% in SCC. Sensitivity and specificity of small cell lung cancer were 25.0%, 78.5% in CEA, 50.0%, 89.6% in Cyfra21-1, 50.0%, 89.6% in TPA-M, 0%, 89.2% in SCC. Cutoff value according to ROC(Receiver operating characteristics) curve was $1.25{\mu}/L$ in CEA, $1.5{\mu}/L$ in Cyfra2-1, 35 U/L in TPA-M, $0.6{\mu}/L$ in SCC. With this cutoff value, sensitivity, specificity, accuracy and kappa index of Cyfra21-1 and TPA-M were better than CEA and SCC. SCC only was related with statistic significance to TNM stages, dividing to operable stages(TNM stage I to IIIA) and inoperable stages (IIIB and IV) (p<0.05). But no tumor markers showed any correlation with significance with tumor size(p>0.05). Conclusion : Serum TPA-M and Cyfra21-1 shows higher sensitivity and specificity than CEA and SCC in overall lung cancer and nonsmall cell lung cancer those were confirmed pathologically. SCC has higher specificity in nonsmall cell lung cancer. And the level of serum sec are signiticantly related with TNM staging.