title: ErbB-4 may control behavior of prostate cancer cells and serve as a target for molecular therapy.
abstract: OBJECTIVE
  To assess ErbB-4 expression in advanced human prostate cancer (PC) cell lines, the role of ErbB-4 in motility, migration, and proliferative/tumorigenic potential of PC cells, and efficacy of anti-ErbB-4 monoclonal antibody (Mab) treatment on PC cells in vitro and tumor growth in vivo.
  
  
  METHODS
  Established advanced human PC cell lines (PC-3, Cl-1, and Du-145) were evaluated for ErbB-4 expression. Several Cl-1 cell line clones expressing various levels of ErbB-4 were isolated, their motility, migration capacity, and in vitro proliferation as well as survival following Mab treatment were evaluated. Tumorigenicity and proliferation capacity of these clones in vivo and efficacy of Mab treatment on tumor growth were estimated by measurements of subcutaneous tumors developed in nude mice.
  
  
  RESULTS
  PC cell lines studied express ErbB-4. Both PC-3 and Du-145 cell lines express high ErbB-4 levels; only 50% of Cl-1 cells express ErbB-4 with large heterogeneity. Cl-1 sub-clones highly expressing ErbB-4 showed increased cell motility, migration, and proliferation rate in vitro and enhanced growth in vivo, compared to clones with low ErbB-4 expression. Mab treatment inhibited the growth of cells expressing high but not low ErbB-4 levels in vitro and decreased the growth of subcutaneous tumors in nude mice generated by ErbB-4 highly expressing cells.
  
  
  CONCLUSIONS
  High expression of ErbB-4 in prostate cancer Cl-1 cell clones correlated with high proliferative and migration capacity and high tumorigenic potential. The inhibitory effect of Mab on cell proliferation and on subcutaneous tumor growth suggests ErbB-4's potential as a target for molecular anticancer therapy.
authors: Department of Oncology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel. ramiby@post.tau.ac.il
authors: Rami
authors: R
authors: Ben-Yosef
authors: Alex
authors: A
authors: Starr
authors: Victoria
authors: V
authors: Karaush
authors: Vered
authors: V
authors: Loew
authors: Shahar
authors: S
authors: Lev-Ari
authors: Itay
authors: I
authors: Barnea
authors: Ghalib
authors: G
authors: Lidawi
authors: Alexander
authors: A
authors: Shtabsky
authors: Yoel
authors: Y
authors: Greif
authors: Yosef
authors: Y
authors: Yarden
authors: Akiva
authors: A
authors: Vexler
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D005562:Formazans / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018739:Oncogene Proteins v-erbB / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D013047:Specific Pathogen-Free Organisms
chemical_list: D000911:Antibodies, Monoclonal; D005562:Formazans; D018739:Oncogene Proteins v-erbB; C059088:1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan