LAT1 regulates growth of uterine leiomyoma smooth muscle cells.
L-type amino acid transporter 1 (LAT1) and LAT2 were shown to encode system L, which mediates the Na(+)-independent transport of branched-chain and aromatic amino acids. We demonstrated previously that LAT2 is a progesterone receptor target gene involved in leiomyoma growth. The role of LAT1 in the regulation of human uterine leiomyoma growth, however, remains unelucidated. We herein investigated the function of LAT1 and its progesterone-mediated regulation within human uterine leiomyoma smooth muscle (LSM) cells (n = 8) and tissues (n = 29). In vivo, LAT1 expression was higher in leiomyoma than in myometrial tissue. LAT1 knockdown augmented cell proliferation and viability. Treatment of LSM cells with RU486 markedly increased LAT1 messenger RNA (mRNA) levels but decreased proliferation in a dose-dependent manner. L-type amino acid transporter 1 as a downstream target, however, did not entirely account for this antiproliferative effect of RU486 on LSM cells. Taken together, LAT1 may have a critical and complex role in regulating human leiomyoma cell growth.
Xia Luo
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Coon
John S
JS
Su
Emily
E
Pearson
Elizabeth Kerry
EK
Ping Yin
Ishikawa
Hiroshi
H
Bulun
Serdar E
SE
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics / Q000378:metabolism*; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009215:Myometrium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D006727:Hormone Antagonists; D027283:Large Neutral Amino Acid-Transporter 1; D012333:RNA, Messenger; D015735:Mifepristone; D011374:Progesterone