Prostate cancer cell proliferation is influenced by leptin

J Surg Res. 2004 May 1;118(1):71-82. doi: 10.1016/j.jss.2004.01.017.


Background: Obesity is considered a risk for many cancers. Serum leptin levels are often elevated in obese people. Leptin acts as a mitogenic agent in many tissues; therefore, it may act to promote cancer cell growth. We previously demonstrated that leptin acts as a growth factor for prostate cancer cells in vitro. The purpose of this study was to characterize leptin receptor isoform mRNA expression in leptin-treated DU145 and PC-3 prostate cancer cell lines. Expression levels of SOCS-3, a known leptin-inducible suppressor of leptin signaling, and known mitogenic signaling pathways of PI3K and ERK were also analyzed

Methods: DU145 and PC-3 cells were treated with 0, 4, 40, or 80 ng/ml leptin for 0, 0.5, 1, 2, 4, 24, or 48 h. Multiplex RT-PCR was performed to determine mRNA levels of the short (huOB-Ra) or the long (huOB-Rb) OB-R isoforms or SOCS-3. p-Akt and p-ERK were determined by Western blot. Cell viability and apoptosis were determined by MTT and nucleosomal fragmentation assay

Results: DU145 and PC-3 expressed huOB-Ra, huOB-Rb, and SOCS-3 mRNA. huOB-Ra mRNA levels increased in PC-3 at 48 h (P < 0.01); however, no significant changes were observed in DU145. huOB-Rb mRNA levels decreased at 48 h in DU145; however, a twofold increase at 48 h (P < 0.01) was observed with PC-3 and was dose-dependent (P < 0.05). Leptin increased SOCS-3 mRNA in DU145 at 24 and 48 h (P < 0.05) and in PC-3 at 1 h (2-fold) and 48 h (fivefold; P < 0.01). Leptin up-regulated p-Akt in a time- and dose-dependent manner in the DU145 prostate cancer cells via a suppression of apoptosis. Leptin up-regulated p-ERK in a time-dependent manner in PC-3 cells

Conclusions: In prostate cancer cells, the mitogenic effects of leptin are not a consequence of altered receptor isoform mRNA expression. No defect in SOCS-3 signaling was observed, and proliferation appears to be working through the PI3K and MAPK leptin receptor-activated pathways, depending on cell type. Leptin stimulation may be selective for either pathway to suppress apoptosis, thereby enhancing prostate cancer growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Enzyme Activation
  • Humans
  • Leptin / administration & dosage
  • Leptin / pharmacology*
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Protein Isoforms / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Leptin
  • Repressor Proteins / genetics
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Transcription Factors / genetics


  • Leptin
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Leptin
  • Repressor Proteins
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Transcription Factors
  • leptin receptor, human
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases