Progesterone and Mifepristone Regulate L-Type Amino Acid Transporter 2 and 4F2 Heavy Chain Expression in Uterine Leiomyoma Cells

Luo, Xia; Yin, Ping; Reierstad, Scott; Ishikawa, Hiroshi; Lin, Zhihong; Pavone, Mary Ellen; Zhao, Hong; Marsh, Erica E.; Bulun, Serdar E.

doi:10.1210/jc.2009-1286

Cited by 25 publications

(23 citation statements)

References 39 publications

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“…Recently, Luo et al [89] defined L-type amino acid transporter 2 (LAT2) as a novel PR target gene. Progesterone significantly induces LAT2 mRNA levels, which is blocked by cotreatment with the PR antagonist mifepristone.…”

Section: Pathogenesis Of Uterine Leiomyomamentioning

confidence: 99%

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

Ciavattini

Giuseppe

Stortoni

et al. 2013

Obstetrics and Gynecology International

167

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Uterine leiomyomas (fibroids or myomas) are benign tumors of uterus and clinically apparent in a large part of reproductive aged women. Clinically, they present with a variety of symptoms: excessive menstrual bleeding, dysmenorrhoea and intermenstrual bleeding, chronic pelvic pain, and pressure symptoms such as a sensation of bloatedness, increased urinary frequency, and bowel disturbance. In addition, they may compromise reproductive functions, possibly contributing to subfertility, early pregnancy loss, and later pregnancy complications. Despite the prevalence of this condition, myoma research is underfunded compared to other nonmalignant diseases. To date, several pathogenetic factors such as genetics, microRNA, steroids, growth factors, cytokines, chemokines, and extracellular matrix components have been implicated in the development and growth of leiomyoma. This paper summarizes the available literature regarding the ultimate relative knowledge on pathogenesis of uterine fibroids and their interactions with endometrium and subendometrial myometrium.

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Section: Pathogenesis Of Uterine Leiomyomamentioning

confidence: 99%

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

Ciavattini

Giuseppe

Stortoni

et al. 2013

Obstetrics and Gynecology International

167

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“…Gene knockdown studies revealed that KLF-11 inhibits proliferation of leiomyoma cells and that its expression is significantly lower in leiomyoma tissues compared with adjacent myometrial tissues. Another novel progesterone receptor target gene identified by ChIP-cloning was the L-type amino acid transporter 2 (LAT2) [132]. Progesterone significantly induced LAT2 mRNA levels, which was blocked by cotreatment with RU486.…”

Section: Regulation Of Genes Associated With Proliferation and Apoptomentioning

confidence: 99%

The role of progesterone signaling in the pathogenesis of uterine leiomyoma

Kim

Sefton

2012

Molecular and Cellular Endocrinology

158

120

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Uterine leiomyomas are benign tumors that originate from the myometrium. Evidence points to ovarian steroid hormones, in particular, progesterone as major promoters of leiomyoma development and growth. While progesterone action in leiomyomas involves the classical nuclear receptor effects on gene regulation, there is growing evidence that signaling pathways are directly activated by the progesterone receptor (PR) and that PR can interact with growth factor signaling systems to promote proliferation and survival of leiomyomas. Studies investigating the genomic and non-genomic actions of PR and its role in leiomyoma growth are summarized here. Studies testing various selective progesterone receptor modulators for the treatment of leiomyomas are also highlighted. An increased understanding of the mechanisms associated with progesterone-driven growth of leiomyomas is critical in order to develop more efficient and targeted therapies for this prevalent disease.

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“…Mifepristone selectively inhibits the formation and development of many tumor types and plays an anti-tumor role as an antagonist through progesterone and glucocorticoid receptors (Kacinski et al, 2001;Luo et al, 2009;Ligr et al, 2012). In this study, 10 mg/mL mifepristone and MMC treatment at different concentrations was applied to HeLa/MMC cells; mifepristone alone had no significant inhibitory effect on the development of HeLa/MMC cells, but both the inhibition rate and drug sensitivity of the cells increased after combination treatment with MMC, indicating that other than anti-tumor activity, mifepristone reverses the drug resistance of tumor cells to some extent.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of the reversal effect of mifepristone on drug resistance of the human cervical cancer cell line HeLa/MMC

Chen¹,

Duan²,

Zuo³

2014

Genet. Mol. Res.

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ABSTRACT. We examined the ability of mifepristone to reverse the in vitro drug resistance of human cervical cancer cells resistant to mitomycin-C (HeLa/MMC) cells and investigated the mechanism of this effect. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the drug resistance of HeLa/ MMC cells and the reversed drug resistance in vitro. Expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and glucosylceramide synthase (GCS) were measured in HeLa and HeLa/ MMC cells. The resistance index of HeLa/MMC cells on MMC was reduced from 5.02 to 1.46 after 10 mg/mL mifepristone exposure. A combination of mifepristone upregulated the Bax/Bcl-2 protein expression ratio and apoptosis in HeLa/MMC cells. GCS expression was significantly higher in HeLa/MMC cells than in HeLa cells (P < 0.01), but distinctly declined in both cell lines after mifepristone application (P < 0.01). Mifepristone reversed the resistance of HeLa/MMC cells to MMC in vitro; the overexpression of the GCS gene and the increased expression of apoptosis-related protein Bcl-2 may play important roles

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Progesterone and Mifepristone Regulate L-Type Amino Acid Transporter 2 and 4F2 Heavy Chain Expression in Uterine Leiomyoma Cells

Cited by 25 publications

References 39 publications

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction

The role of progesterone signaling in the pathogenesis of uterine leiomyoma

Mechanism of the reversal effect of mifepristone on drug resistance of the human cervical cancer cell line HeLa/MMC

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