Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer.
S100P is a member of the S100 family of calcium-binding proteins and there have been several recent reports of its overexpression in pancreatic ductal adenocarcinoma (PDAC). We have used Far Western screening and in vitro interaction assays to identify and confirm a novel target protein for S100P. We have named this protein S100PBPR, and shown that its interaction with S100P is dependent on Ca(2+) or Mg(2+). S100PBPR was found to localize to cell nuclei where S100P is also present, and the two proteins co-immunoprecipitate. By in situ hybridization, S100PBPR transcript was found in islet cells but not duct cells of the healthy pancreas. Both S100P and S100PBPR were detected by quantitative real-time polymerase chain reaction in pancreatic intraepithelial neoplasia (PanIN) and PDAC samples, and in situ hybridization revealed the presence of S100PBPR transcript in malignant PDAC cells. These data suggest that an interaction between S100P and S100PBPR may be involved in early pancreatic cancer. S100P was further investigated in PanIN lesions and immunohistochemical analysis showed its expression to correlate significantly with increasing grade of PanINs, being found as early as PanIN-1 with more prevalent expression in PanIN-2 and -3. These data suggest that S100P can be added to the genetic progression model for PDAC.
Dowen
Sally E
SE
Molecular Oncology Unit, Barts and The London School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.
Crnogorac-Jurcevic
Tatjana
T
Gangeswaran
Rathi
R
Hansen
Mikkel
M
Eloranta
Jyrki J
JJ
Bhakta
Vipul
V
Brentnall
Teresa A
TA
Lüttges
Jutta
J
Klöppel
Gunther
G
Lemoine
Nick R
NR
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D017931:DNA Primers; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008274:Magnesium / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C103003:S100P protein, human; C496889:S100PBP protein, human; D008274:Magnesium; D002118:Calcium