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[New insight into the mechanism of p53 inducing leukemia cell apoptosis].
Zhonghua Xue Ye Xue Za Zhi. 2003 Dec; 24(12):640-3.ZX

Abstract

OBJECTIVE

To investigate the expression changes of intrinsic cytokines TGF-beta(1) and TNF-alpha, telomerase activity and bcl-2 during ongoing apoptosis of HL-60 and K562 cells induced by p53.

METHODS

pN53cG (Val135), a temperature sensitive p53 mutant, which behaved like wild type p53 (wt-p53) at 32.5 degrees C, were introduced into p53-null HL-60 and K562 cells respectively by lipofectin. In the presence of G418, HL-60-pN53cG and K562 pN53cG clones expressing p53 protein were selected. The ongoing expression of intrinsic cytokines (TGF-beta(1) and TNF-alpha), bcl-2 oncogene and hTERT mRNA during the apoptosis of HL-60 and K562 cells induced by p53 and the effects of exogenous p53 gene, TGF-beta(1) and TNF-alpha antisense PS-ODNS on the apoptosis of HL-60 and K562 cells and the expression of bcl-2 were studied by RT-PCR, quantitative RT-PCR, DNA fragmentation, TdT-mediated dUTP nick end labeling (TUNEL) and flow cytometery. The levels of secreted TGF-beta(1) and telomerase activity were detected by ELISA and PCR-ELISA, respectively.

RESULTS

(1) The expressions of intrinsic TGF-beta(1) and TNF-alpha mRNA were up-regulated, while that of bcl-2 and hTERT down-regulated. The levels of TGF-beta(1) in the supernatant of HL-60 and K562 cells were increased, and the level of telomerase activity decreased. (2) Antisense PS-ODNS of TGF-beta(1) and TNF-alpha could obviously inhibit the p53 inducing cell apoptosis, and restore bcl-2 mRNA and protein to pre-treated level.

CONCLUSIONS

Exogenous p53 induces leukemia cell apoptosis via up-regulating the expression of intrinsic TGF-beta(1) and TNF-alpha and down-regulating the expression of hTERT and bcl-2.

Authors+Show Affiliations

Fujian Institute of Hematology, Union Hospital, Fujian Medical University, Fuzhou 350001, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

14761612

Citation

Chen, Yuan-zhong, et al. "[New Insight Into the Mechanism of P53 Inducing Leukemia Cell Apoptosis]." Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi, vol. 24, no. 12, 2003, pp. 640-3.
Chen YZ, Wu Y, Liang M, et al. [New insight into the mechanism of p53 inducing leukemia cell apoptosis]. Zhonghua Xue Ye Xue Za Zhi. 2003;24(12):640-3.
Chen, Y. Z., Wu, Y., Liang, M., Li, N. N., Zhang, Z. X., & Lu, L. H. (2003). [New insight into the mechanism of p53 inducing leukemia cell apoptosis]. Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi, 24(12), 640-3.
Chen YZ, et al. [New Insight Into the Mechanism of P53 Inducing Leukemia Cell Apoptosis]. Zhonghua Xue Ye Xue Za Zhi. 2003;24(12):640-3. PubMed PMID: 14761612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [New insight into the mechanism of p53 inducing leukemia cell apoptosis]. AU - Chen,Yuan-zhong, AU - Wu,Yong, AU - Liang,Min, AU - Li,Nai-nong, AU - Zhang,Zhao-xiu, AU - Lu,Lian-huang, PY - 2004/2/6/pubmed PY - 2004/5/13/medline PY - 2004/2/6/entrez SP - 640 EP - 3 JF - Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi JO - Zhonghua Xue Ye Xue Za Zhi VL - 24 IS - 12 N2 - OBJECTIVE: To investigate the expression changes of intrinsic cytokines TGF-beta(1) and TNF-alpha, telomerase activity and bcl-2 during ongoing apoptosis of HL-60 and K562 cells induced by p53. METHODS: pN53cG (Val135), a temperature sensitive p53 mutant, which behaved like wild type p53 (wt-p53) at 32.5 degrees C, were introduced into p53-null HL-60 and K562 cells respectively by lipofectin. In the presence of G418, HL-60-pN53cG and K562 pN53cG clones expressing p53 protein were selected. The ongoing expression of intrinsic cytokines (TGF-beta(1) and TNF-alpha), bcl-2 oncogene and hTERT mRNA during the apoptosis of HL-60 and K562 cells induced by p53 and the effects of exogenous p53 gene, TGF-beta(1) and TNF-alpha antisense PS-ODNS on the apoptosis of HL-60 and K562 cells and the expression of bcl-2 were studied by RT-PCR, quantitative RT-PCR, DNA fragmentation, TdT-mediated dUTP nick end labeling (TUNEL) and flow cytometery. The levels of secreted TGF-beta(1) and telomerase activity were detected by ELISA and PCR-ELISA, respectively. RESULTS: (1) The expressions of intrinsic TGF-beta(1) and TNF-alpha mRNA were up-regulated, while that of bcl-2 and hTERT down-regulated. The levels of TGF-beta(1) in the supernatant of HL-60 and K562 cells were increased, and the level of telomerase activity decreased. (2) Antisense PS-ODNS of TGF-beta(1) and TNF-alpha could obviously inhibit the p53 inducing cell apoptosis, and restore bcl-2 mRNA and protein to pre-treated level. CONCLUSIONS: Exogenous p53 induces leukemia cell apoptosis via up-regulating the expression of intrinsic TGF-beta(1) and TNF-alpha and down-regulating the expression of hTERT and bcl-2. SN - 0253-2727 UR - https://www.unboundmedicine.com/medline/citation/14761612/[New_insight_into_the_mechanism_of_p53_inducing_leukemia_cell_apoptosis]_ DB - PRIME DP - Unbound Medicine ER -