CEBPD suppresses prolactin expression and prolactinoma cell proliferation

Yunguang Tong, Jin Zhou, Jun Mizutani, Hidenori Fukuoka, Song Guang Ren, Arthur Gutierrez-Hartmann, H. Phillip Koeffler, Shlomo Melmed

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Hyperprolactinemia, usually caused by a pituitary lactotroph tumor, leads to galactorrhea and infertility. Increased prolactin (PRL) levels may be due to enhanced PRL expression or proliferation of PRL-secreting cells. We hypothesize that PRL expression and PRL-secreting cell proliferation are linked. Using microarray-based gene expression profiling, we identified CCAAT-enhancer-binding protein δ (CEBPD) transcription factor as a critical gene that regulates both PRL expression and lactotroph cell proliferation. CEBPD expression levels are decreased approximately 7-fold in experimental rat prolactinoma cells. Forced expression of this transcription factor in PRL-secreting cells (GH3 and MMQ) inhibited PRL expression and cellular proliferation, and CEBPD knockdown by small interfering RNA leads to increased PRL expression in both cell lines. To determine mechanisms underlying this observation, we determined binding of CEBPD to the PRL promoter and also showed marked suppression (96%) of PRL promoter activity. CEBPD and Pit1 interact and attenuate each other's binding to the PRL promoter. CEBPD also suppresses expression of proliferation-related genes, including c-Myc, survivin, as well as cyclins B1, B2, and D1. These results show that PRL expression and cell proliferation are controlled in part by CEBPD.

Original languageEnglish (US)
Pages (from-to)1880-1891
Number of pages12
JournalMolecular Endocrinology
Volume25
Issue number11
DOIs
StatePublished - Nov 1 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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    Tong, Y., Zhou, J., Mizutani, J., Fukuoka, H., Ren, S. G., Gutierrez-Hartmann, A., Phillip Koeffler, H., & Melmed, S. (2011). CEBPD suppresses prolactin expression and prolactinoma cell proliferation. Molecular Endocrinology, 25(11), 1880-1891. https://doi.org/10.1210/me.2011-1075