Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells

Guangli Suo; Anil Sadarangani; Wingchung Tang; Bryan D Cowan; Jean Y J Wang

doi:10.1177/1933719114532839

Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells

Reprod Sci. 2014 Sep;21(9):1161-70. doi: 10.1177/1933719114532839. Epub 2014 Apr 30.

Authors

Guangli Suo¹, Anil Sadarangani², Wingchung Tang², Bryan D Cowan³, Jean Y J Wang⁴

Affiliations

¹ Department of Medicine, Division of Hematology/Oncology, Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA [email protected].
² Department of Medicine, Division of Hematology/Oncology, Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA.
³ Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USA.
⁴ Department of Medicine, Division of Hematology/Oncology, Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA [email protected].

Abstract

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.

Keywords: leiomyoma; rapamycin; telomerase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Cycle Checkpoints / drug effects
Cell Cycle Checkpoints / physiology
Cell Line, Transformed
Cells, Cultured
Female
Growth Inhibitors / pharmacology*
Growth Inhibitors / therapeutic use
Humans
Leiomyoma / drug therapy
Leiomyoma / enzymology*
Leiomyoma / pathology
Mechanistic Target of Rapamycin Complex 1
Mice
Mice, Knockout
Multiprotein Complexes / antagonists & inhibitors
Multiprotein Complexes / metabolism
Myocytes, Smooth Muscle / drug effects
Myocytes, Smooth Muscle / enzymology*
Myocytes, Smooth Muscle / pathology
Sirolimus / antagonists & inhibitors
Sirolimus / pharmacology*
Sirolimus / therapeutic use
TOR Serine-Threonine Kinases / antagonists & inhibitors
TOR Serine-Threonine Kinases / metabolism
Telomerase / biosynthesis*
Uterine Neoplasms / drug therapy
Uterine Neoplasms / enzymology*
Uterine Neoplasms / pathology

Substances

Growth Inhibitors
Multiprotein Complexes
Mechanistic Target of Rapamycin Complex 1
TOR Serine-Threonine Kinases
TERT protein, human
Telomerase
Sirolimus

Abstract

Publication types

MeSH terms

Substances

Grants and funding