, Volume 46, Issue 3, pp 568–576 | Cite as

Knockdown of prolactin receptors in a pancreatic beta cell line: effects on DNA synthesis, apoptosis, and gene expression

  • Ramamani ArumugamEmail author
  • Don Fleenor
  • Michael FreemarkEmail author
Original Article


Prolactin (PRL) and placental lactogen stimulate beta cell replication and insulin production in vitro and in vivo. The molecular mechanisms by which lactogens promote beta cell expansion are unclear. We treated rat insulinoma cells with a PRL receptor (PRLR) siRNA to determine if PRLR signaling is required for beta cell DNA synthesis and cell survival and to identify beta cell cycle genes whose expression depends upon lactogen action. Effects of PRLR knockdown were compared with those of PRL treatment. PRLR knockdown (−80 %) reduced DNA synthesis, increased apoptosis, and inhibited expression of cyclins D2 and B2, IRS-2, Tph1, and the anti-apoptotic protein PTTG1; p21 and BCL6 mRNAs increased. Conversely, PRL treatment increased DNA synthesis, reduced apoptosis, and enhanced expression of A, B and D2 cyclins, CDK1, IRS-2, FoxM1, BCLxL, and PTTG1; BCL6 declined. PRLR signaling is required for DNA synthesis and survival of rat insulinoma cells. The effects of lactogens are mediated by down-regulation of cell cycle inhibitors (BCL6, p21) and induction of A, B, and D2 cyclins, IRS-2, Tph1, FoxM1, and the anti-apoptotic proteins BCLxL and PTTG1.


Lactogen Cyclin BCL6 PTTG1 IRS-2 FoxM1 



The authors thank the National Hormone & Peptide program and Dr. A.F. Parlow, Scientific Director for providing rat PRL. These studies were supported by grants from the NICHD (HD024192) and the American Diabetes Association (7-08-RA-46) (to MF), the Duke Children’s Miracle Network (to RA), and Duke’s Neonatal Perinatal Research Institute.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Pediatric Endocrinology & DiabetesDuke University Medical CenterDurhamUSA
  2. 2.Department of Cell BiologyDuke University Medical CenterDurhamUSA

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