Original Article

Virchows Archiv

, Volume 453, Issue 6, pp 557-569

Estrogen receptor alpha (ERα) phospho-serine-118 is highly expressed in human uterine leiomyomas compared to matched myometrium

  • Tonia L. HermonAffiliated withCellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences (NIEHS), National Toxicology Program (NTP), National Institutes of Health (NIH), Department of Health and Human Services (DHHS)Department of Physiological Sciences, Division of Biochemistry, Eastern Virginia Medical School
  • , Alicia B. MooreAffiliated withCellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences (NIEHS), National Toxicology Program (NTP), National Institutes of Health (NIH), Department of Health and Human Services (DHHS)
  • , Linda YuAffiliated withCellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences (NIEHS), National Toxicology Program (NTP), National Institutes of Health (NIH), Department of Health and Human Services (DHHS)
  • , Grace E. KisslingAffiliated withBiostatistics Branch, National Institute of Environmental Health Sciences (NIEHS), National Toxicology Program (NTP), National Institutes of Health (NIH), Department of Health and Human Services (DHHS)
  • , Frank J. CastoraAffiliated withDepartment of Physiological Sciences, Division of Biochemistry, Eastern Virginia Medical School
  • , Darlene DixonAffiliated withCellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences (NIEHS), National Toxicology Program (NTP), National Institutes of Health (NIH), Department of Health and Human Services (DHHS) Email author 

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Abstract

It is thought that the growth of uterine leiomyomas may be mediated by the interaction of estrogen receptor alpha (ERα) and growth factor pathways and that phosphorylation of ERα at serine 118 (ERα-phospho-Ser118) is important in this interaction. In this study, immunoblotting and immunohistochemistry were used to investigate the expression of ERα-phospho-Ser118, phosphorylated p44/42 mitogen-activated protein kinase (phospho-p44/42 MAPK), and proliferating cell nuclear antigen (PCNA) in human leiomyoma and myometrial tissues during the proliferative and secretory phases of the menstrual cycle. We found that tumors taken from the proliferative phase expressed significantly higher levels of ERα-phospho-Ser118, phospho-p44/42 MAPK, and PCNA compared to patient-matched myometria and had significantly higher ERα-phospho-Ser118 and PCNA expression compared to secretory phase tumors. Also, enhanced colocalization and association of phospho-p44/42 MAPK and ERα-phospho-Ser118 were observed in proliferative phase tumors by confocal microscopy and immunoprecipitation, respectively. These data suggest that ERα-phospho-Ser118 may be important in leiomyoma growth and is possibly phosphorylated by phospho-p44/42 MAPK.

Keywords

Uterine leiomyoma Estrogen receptor alpha phosphorylated serine 118 Phosphorylated mitogen-activated protein kinase