The expression of telomeric proteins and their probable regulation of telomerase during the differentiation of all-trans-retinoic acid-responsive and -resistant acute promyelocytic leukemia cells.
Telomerase activity has been linked to retinoid induction of tumor cell differentiation, and the patterns of telomerase expression are different in the 2 pathways of acute promyelocytic leukemia (APL) cell differentiation: the retinoic acid receptor 3 (RAR3)-dependent and the retinoic X receptor 3 (RXR3)-dependent pathways. Still, whether telomeric proteins respond to retinoid treatment is not clear. If they do, how they would respond and how they would interfere in telomerase regulation during differentiation are also unclear. Using all-trans-retinoic acid (ATRA)-sensitive and -resistant APL cell lines NB4, NB4-R1, and NB4-R2, we analyzed a panel of telomeric proteins, including TRF1, PINX1, TANK1, and TANK2, at the messenger RNA (mRNA) and protein expression levels during the differentiation of these cell lines in the 2 pathways. Our analyses showed that both mRNA and protein expression of TRF1 remained stable during NB4 and NB4-R1 cell differentiation but slightly increased in NB4-R2 cells, suggesting that TRF1 may have different functions in the RAR3- and RXR3-dependent pathways. The stable expression of TRF1 may be because telomere length remains unchanged. Pinx1 mRNA expression was tightly correlated with telomerase reverse transcriptase (hTERT) mRNA expression during differentiation. Variation in Pinx1 expression may be a reaction induced by hTERT expression variation. TANK1 mRNA expression and TANK1 protein levels were both down-regulated in all 3 APL cell lines at a later period of differentiation, suggesting that TANK1 may positively regulate telomerase activity and that both RAR3- and RXR3-dependent pathways may exert this regulation.TANK2 expression levels remained stable in all 3 APL cell lines during differentiation, showing that TANK2 may have little effect on telomerase. Thus, our studies provide an outline of the dynamics of telomeric protein expression and the probable regulatory effects of these proteins on telomerase during the differentiation of ATRA-responsive and -resistant APL cells.
Sun
Jie
J
Department of Hematology, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Huang
He
H
Zhu
Yuanyuan
Y
Lan
Jianping
J
Li
Jingyuan
J
Lai
Xiaoyu
X
Yu
Jian
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D038501:Tankyrases / Q000096:biosynthesis*; D019098:Telomerase / Q000096:biosynthesis*; D035321:Telomeric Repeat Binding Protein 1 / Q000096:biosynthesis*; D014212:Tretinoin / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047490:Retinoid X Receptor alpha; D038501:Tankyrases; D019098:Telomerase; D035321:Telomeric Repeat Binding Protein 1; D014212:Tretinoin; D025521:Tumor Suppressor Proteins; C440808:PINX1 protein, human; C418109:TNKS protein, human