PACAP(6-38) is a PACAP receptor antagonist for breast cancer cells

Breast Cancer Res Treat. 1999 Jul;56(2):177-86. doi: 10.1023/a:1006262611290.


The effects of pituitary adenylate cyclase activating polypeptide (PACAP) analogs were investigated using breast cancer cells. 125I-PACAP-27 bound with high affinity (Kd = 5 nM) to T47D cells (Bmax = 29,000 per cell). Specific 125I-PACAP-27 binding was inhibited half maximally by PACAP-27, PACAP-38, PACAP(6-38) and PACAP(28-38) with IC50) values of 8, 17, 750 and >3000 nM, respectively. By RT-PCR, PACAP receptor mRNA was present in MCF-7 and T47D cell lines. Polyclonal antibodies to a PACAP receptor fragment (A-8-C) were elicited. The antibodies were affinity purified, recognized a 60-kDa protein by western blot, and stained malignant cells in breast cancer biopsy specimens by immunohistochemistry. PACAP-27 elevated the cAMP in T47D cells and the increase in cAMP caused by PACAP was inhibited by PACAP(6-38). PACAP-27 stimulated c-fos mRNA in T47D cells and the increase in c-fos gene expression caused by PACAP was reversed by PACAP(6-38). PACAP(6-38) inhibited colony formation using a soft agar assay and inhibited breast cancer xenograft growth in nude mice. These data suggest that PACAP(6-38) functions as a breast cancer PACAP receptor antagonist.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • Female
  • Growth Inhibitors / metabolism
  • Growth Inhibitors / pharmacology
  • Humans
  • Mammary Neoplasms, Experimental / enzymology
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Neuropeptides / antagonists & inhibitors
  • Neuropeptides / metabolism
  • Neuropeptides / pharmacology*
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Rabbits
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Hormone / antagonists & inhibitors*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • Growth Inhibitors
  • Neuropeptides
  • Peptide Fragments
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Hormone
  • pituitary adenylate-cyclase-activating-peptide (6-38)