title: Anti-patched-1 antibodies suppress hedgehog signaling pathway and pancreatic cancer proliferation.
abstract: BACKGROUND
  The hedgehog (Hh) signaling pathway is aberrantly activated in many human carcinomas including pancreatic cancer and regulates tumor cell growth. Overproduction of sonic hedgehog (Shh), a ligand of the Hh signaling pathway, increases the Hh signaling activity through transmitting the signal to patched-1 (Ptch1), the receptor of the Hh signaling pathway.
  
  
  METHODS
  a-Ptch1 antibodies were raised against an oligo-peptide, designed according to the Ptch1 aminoacid sequence. The specificity of a-Ptch1 was examined by immunoblotting and immuno-fluorescence, and biological effects were detected by RT-PCR and cell proliferation assay using two pancreatic cancer cell lines, Panc1 and SUIT-2.
  
  
  RESULTS
  a-Ptch1 recognized a 160 kDa protein as shown by immunoblotting and cell surface staining of pancreatic cancer cells. Incubation with a-Ptch1 suppressed Hh signaling activity and proliferation of pancreatic cancer cells.
  
  
  CONCLUSIONS
  These results provide a new strategy for controling Hh dependent development of pancreatic cancer and other Hh related carcinomas.
authors.affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. mnaka@surg1.med.kyushu-u.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubo
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yanai
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Mikami
authors.forename: Mio
authors.initials: M
authors.lastname: Ikebe
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Nagai
authors.forename: Koji
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D000906:Antibodies / Q000494:pharmacology*; D000918:Antibody Specificity; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000906:Antibodies; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface