title: Fas ligand expression and its correlation with apoptosis and proliferation in Lobund-Wistar prostate carcinomas.
abstract: OBJECTIVE
  The Fas (CD95) interaction with its receptor Fas ligand (FasL) is one of the main mechanisms of cell apoptosis. High expression of FasL has been consistently observed in a variety of human cancers. In this study, we evaluated FasL and its relationship with apoptosis and proliferation in Lobund-Wistar (L-W) cancers. The L-W rat strain develops spontaneous and induced adenocarcinomas in the anterior prostate and seminal vesicles. Although FasL expression has been observed in a subset of human prostate carcinomas, this multistage model allowed in vivo evaluation of subclones of malignant cells with a single genetic susceptibility.
  
  
  METHODS
  Apoptosis was evaluated in spontaneous, induced and transplanted tumors as well as metastasis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique and transmission electron microscopy. Proliferating cell nuclear antigen (PCNA) and FasL expression were detected using immunohistochemistry and analyzed according to the number of positive cells and intensity of staining using a semiquantitive method.
  
  
  RESULTS
  Apoptotic indexes were significantly higher in spontaneous tumors compared to induced (p < 0.008), transplanted tumors (p < 0.0112) and metastases (p < 0.009). TUNEL-positive cells were frequently observed in the leukocytic infiltrate of the stroma in transplanted carcinomas and metastases. These findings were confirmed by electron microscopy. FasL expression was not uniformly localized in L-W carcinomas and its highest expression was observed in transplanted tumors and metastasis (p < 0.005). Moreover, PCNA indices were directly correlated with cancers showing high FasL total scores (Hscores).
  
  
  CONCLUSIONS
  In this model, high FasL expression was associated with cells displaying low apoptotic indexes and high PCNA index. Therefore, analysis of FasL may have clinical relevance in detecting the malignant potential of prostate cancers.
authors.affiliation: Walther Cancer Center, Notre Dame, IN, USA. gutierre@wilkes.edu
authors.forename: Linda S
authors.initials: LS
authors.lastname: Gutierrez
authors.forename: Francisco
authors.initials: F
authors.lastname: Noria
authors.forename: Hector
authors.initials: H
authors.lastname: Finol
authors.forename: Longhua
authors.initials: L
authors.lastname: Sun
authors.forename: Francis
authors.initials: F
authors.lastname: Castellino
authors.forename: Morris
authors.initials: M
authors.lastname: Pollard
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism* / Q000556:secondary; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D022083:Cytoplasmic Structures / Q000187:drug effects / Q000648:ultrastructure; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D020287:In Situ Nick-End Labeling; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012669:Seminal Vesicles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048069:Tumor Necrosis Factors / Q000378:metabolism*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D018809:Proliferating Cell Nuclear Antigen; D048069:Tumor Necrosis Factors