ArticleThe Journal of clinical endocrinology and metabolism2009
Progesterone and mifepristone regulate L-type amino acid transporter 2 and 4F2 heavy chain expression in uterine leiomyoma cells.
Article in The Journal of clinical endocrinology and metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Targeting LAT1 with JPH203 to reduce TNBC proliferation and reshape suppressive immune microenvironment by blocking essential amino acid uptake.Amino acids · 2025Article
- Progesterone signaling in uterine fibroids: Molecular mechanisms and therapeutic opportunities.Life sciences · 2025Review
- Article
- Mono-(2-ethyl-5-hydroxyhexyl) phthalate promotes uterine leiomyoma cell survival through tryptophan-kynurenine-AHR pathway activation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Protein kinase C activation upregulates human L-type amino acid transporter 2 function.The journal of physiological sciences : JPS · 2021Article
- Selective Progesterone Receptor Modulators-Mechanisms and Therapeutic Utility.Endocrine reviews · 2020Review
- The solute carrier SLC7A8 is a marker of favourable prognosis in ER-positive low proliferative invasive breast cancer.Breast cancer research and treatment · 2020Article
- Mifepristone inhibits IGF-1 signaling pathway in the treatment of uterine leiomyomas.Drug design, development and therapy · 2019Article
- LAT2 regulates glutamine-dependent mTOR activation to promote glycolysis and chemoresistance in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2018Article
- L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia.American journal of cancer research · 2015Review
- Comparison of the inhibitory effect of gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM), antiprogesterone on myoma cell proliferation in vitro.International journal of medical sciences · 2014Article
- Article
- Uterine fibroids: pathogenesis and interactions with endometrium and endomyometrial junction.Obstetrics and gynecology international · 2013Review
- The role of progesterone signaling in the pathogenesis of uterine leiomyoma.Molecular and cellular endocrinology · 2012Review
- Proceedings from theNational Institute of Child Health and Human Development conference on the Uterine Fibroid Research Update Workshop.Fertility and sterility · 2011Article
- The selective progesterone receptor modulator CDB4124 inhibits proliferation and induces apoptosis in uterine leiomyoma cells.Fertility and sterility · 2010Article
- Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: comprehensive review, conference summary and future recommendations.Human reproduction updateArticle
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
contextProgesterone and its receptor (PR) play key roles in uterine leiomyoma growth. Previously, using chromatin immunoprecipitation-based cloning, we uncovered L-type amino acid transporter 2 (LAT2) as a novel PR target gene. LAT2 forms heterodimeric complexes with 4F2 heavy chain (4F2hc), a single transmembrane domain protein essential for LAT2 to exert its function in the plasma membrane. Until now, little is known about the roles of LAT2/4F2hc in the regulation of the growth of human uterine leiomyoma.
objectiveThe aim of the study is to investigate the regulation of LAT2 and 4F2hc by progesterone and the antiprogestin mifepristone and their functions in primary human uterine leiomyoma smooth muscle (LSM) cells and tissues from 39 premenopausal women.
resultsIn primary LSM cells, progesterone significantly induced LAT2 mRNA levels, and this was blocked by cotreatment with mifepristone. Progesterone did not alter 4F2hc mRNA levels, whereas mifepristone significantly induced 4F2hc mRNA expression. Small interfering RNA knockdown of LAT2 or 4F2hc markedly increased LSM cell proliferation. LAT2, PR-B, and PR-A levels were significantly higher in freshly isolated LSM cells vs. adjacent myometrial cells. In vivo, mRNA levels of LAT2 and PR but not 4F2hc were significantly higher in leiomyoma tissues compared with matched myometrial tissues.
conclusionWe present evidence that progesterone and its antagonist mifepristone regulate the amino acid transporter system LAT2/4F2hc in leiomyoma tissues and cells. Our findings suggest that products of the LAT2/4F2hc genes may play important roles in leiomyoma cell proliferation. We speculate that critical ratios of LAT2 to 4F2hc regulate leiomyoma growth.
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