Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells.
Uterine fibroids are the most common solid tumors found in women of reproductive age. It has been reported that deregulation of the mammalian target of rapamycin (mTOR) pathway plays an important role in the etiology of leiomyoma. Here, we investigated the effect of rapamycin, an inhibitor of mTORC1, on the growth of primary fibroid smooth muscle cells (fSMCs) and human telomerase reverse transcriptase (hTERT)-transduced and immortalized fSMCs. With the primary fSMCs, a 24-hour treatment with rapamycin was sufficient to trigger a growth arrest that was not reversible upon drug removal. By contrast, the growth inhibitory effect of rapamycin on the hTERT-transduced fSMCs was readily reversible, as these cells resumed proliferation upon the withdrawal of the drug. These results suggest that rapamycin-induced irreversible growth arrest of fSMCs is dependent on the senescence barrier that is abrogated by the ectopic expression of telomerase.
Department of Medicine, Division of Hematology/Oncology, Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA glsuo2013@sinano.ac.cn.
Guangli
G
Suo
Department of Medicine, Division of Hematology/Oncology, Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Anil
A
Sadarangani
Department of Medicine, Division of Hematology/Oncology, Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Wingchung
W
Tang
Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USA.
Bryan D
BD
Cowan
Department of Medicine, Division of Hematology/Oncology, Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA jywang@ucsd.edu.
Jean Y J
JY
Wang
D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D020123:Sirolimus / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019098:Telomerase / Q000096:biosynthesis*; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D006131:Growth Inhibitors; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; C509186:TERT protein, human; D019098:Telomerase; D020123:Sirolimus
leiomyoma; rapamycin; telomerase