Alternative Splicing of Human Telomerase Reverse Transcriptase May Not Be Involved in Telomerase Regulation During all-trans-Retinoic Acid-Induced HL-60 Cell Differentiation

Journal of Pharmacological Sciences

Zhi-Xiang Zhang¹  Wei-Jun Liu¹  Jian Ding¹  Yong-Wei Zhang¹ 

[1] Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

关键词: telomerase;    human telomerase reverse transcriptase;    alternative splicing;    differentiation;    all-trans-retinoic acid;   

DOI  :  10.1254/jphs.FP0030600

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(39)Cited-By(9)Alternative splicing of the human telomerase reverse transcriptase subunit (hTERT) suppresses telomerase activity during the development of human fetal kidney cells into mature cells. Tumor cell differentiation is the process of turning abnormal tumor cells into ‘normal’ cells accompanied by down-regulation of telomerase activity. However, the precise mechanism of the regulation of telomerase activity in differentiated cells is not fully understood. In this study, we observed the role of alternative splicing of hTERT in the regulation of telomerase activity in all-trans-retinoic acid (ATRA)-induced, differentiated HL-60 cells. ATRA-induced down-regulation of telomerase activity in differentiated HL-60 cells was associated with a decrease in hTERT and an increase in human telomerase-associated protein-1 (hTP1) transcription. Expression of full length variant hTERT α+β+ mRNA decreased in a dose- and time-dependent manner. The drop of hTERT β− mRNA was time-dependent. hTERT α− and hTERT α−β− mRNA were reduced dramatically after ATRA treatment. In the dose-effect study, hTERT α+β+ and hTERT β− maintained a relatively stable ratio when telomerase activity decreased largely from treatment with 1 to 5 μM ATRA. Although the splicing pattern of hTERT mRNA was altered in time-effect research, the change was not related to the ATRA-treated decline of telomerase activity. The expression of alternative splicing variants of hTERT also decreased at the protein level. All these results suggested that alternative splicing of hTERT mRNA may not contribute to the suppression of telomerase activity during ATRA-induced HL-60 leukemia cell differentiation.

【 授权许可】

Unknown