Expression profiling of nuclear receptors identifies key roles of NR4A subfamily in uterine fibroids

Hanwei Yin, Jay H. Lo, Ji Young Kim, Erica E Marsh, J Julie Kim, Asish K Ghosh, Serdar E Bulun, Debabrata Chakravarti

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Uterine fibroids (UFs), also known as uterine leiomyomas, are benign, fibrotic smooth muscle tumors. Although the GnRH analog leuprolide acetate that suppresses gonadal steroid hormones is used as a treatment, it has significant side effects, thereby limiting its use. Availability of more effective therapy is limited because of a lack of understanding of molecular underpinnings of the disease. Although ovarian steroid hormones estrogen and progesterone and their receptors are clearly involved, the role of other nuclear receptors (NRs) in UFs is not well defined. We used quantitative real-time PCR to systematically profile the expression of 48 NRs and identified several NRs that were aberrantly expressed in UFs. Among others, expression of NR4A subfamily members including NGFIB (NR4A1), NURR1 (NR4A2), and NOR1 (NR4A3) were dramatically suppressed in leiomyoma compared with the matched myometrium. Restoration of expression of each of these NR4A members in the primary leiomyoma smooth muscle cells decreased cell proliferation. Importantly, NR4As regulate expressions of the profibrotic factors including TGFβ 3 and SMAD3, and several collagens that are key components of the extracellular matrix. Finally, we identify NR4A members as targets of leuprolide acetate treatment. Together, our results implicate several NRs including the NR4A subfamily in leiomyoma etiology and identify NR4As as potential therapeutic targets for treating fibrotic diseases.

Original languageEnglish (US)
Pages (from-to)726-740
Number of pages15
JournalMolecular Endocrinology
Volume27
Issue number5
DOIs
StatePublished - May 1 2013

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Leiomyoma
Cytoplasmic and Nuclear Receptors
Leuprolide
Smooth Muscle Tumor
Myometrium
Gonadal Steroid Hormones
Progesterone Receptors
Gonadotropin-Releasing Hormone
Smooth Muscle Myocytes
Extracellular Matrix
Real-Time Polymerase Chain Reaction
Estrogens
Collagen
Steroids
Cell Proliferation
Hormones
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

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title = "Expression profiling of nuclear receptors identifies key roles of NR4A subfamily in uterine fibroids",
abstract = "Uterine fibroids (UFs), also known as uterine leiomyomas, are benign, fibrotic smooth muscle tumors. Although the GnRH analog leuprolide acetate that suppresses gonadal steroid hormones is used as a treatment, it has significant side effects, thereby limiting its use. Availability of more effective therapy is limited because of a lack of understanding of molecular underpinnings of the disease. Although ovarian steroid hormones estrogen and progesterone and their receptors are clearly involved, the role of other nuclear receptors (NRs) in UFs is not well defined. We used quantitative real-time PCR to systematically profile the expression of 48 NRs and identified several NRs that were aberrantly expressed in UFs. Among others, expression of NR4A subfamily members including NGFIB (NR4A1), NURR1 (NR4A2), and NOR1 (NR4A3) were dramatically suppressed in leiomyoma compared with the matched myometrium. Restoration of expression of each of these NR4A members in the primary leiomyoma smooth muscle cells decreased cell proliferation. Importantly, NR4As regulate expressions of the profibrotic factors including TGFβ 3 and SMAD3, and several collagens that are key components of the extracellular matrix. Finally, we identify NR4A members as targets of leuprolide acetate treatment. Together, our results implicate several NRs including the NR4A subfamily in leiomyoma etiology and identify NR4As as potential therapeutic targets for treating fibrotic diseases.",
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Expression profiling of nuclear receptors identifies key roles of NR4A subfamily in uterine fibroids. / Yin, Hanwei; Lo, Jay H.; Kim, Ji Young; Marsh, Erica E; Kim, J Julie; Ghosh, Asish K; Bulun, Serdar E; Chakravarti, Debabrata.

In: Molecular Endocrinology, Vol. 27, No. 5, 01.05.2013, p. 726-740.

Research output: Contribution to journalArticle

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T1 - Expression profiling of nuclear receptors identifies key roles of NR4A subfamily in uterine fibroids

AU - Yin, Hanwei

AU - Lo, Jay H.

AU - Kim, Ji Young

AU - Marsh, Erica E

AU - Kim, J Julie

AU - Ghosh, Asish K

AU - Bulun, Serdar E

AU - Chakravarti, Debabrata

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