Tissue expression of neu differentiation factor/heregulin and its receptor complex in prostate cancer and its biologic effects on prostate cancer cells in vitro.

摘要: BACKGROUND Prostate cancer is the most common in American men and second leading cause of death. All clinical observations correlate poorly differentiated high-grade prostate with disease-specific mortality. The HER2 cell membrane tyrosine kinase, a member epidermal growth factor receptor family that transcription product erbB2neu oncogene, HER3, protein same family, are overexpressed prostatic intraepithelial neoplasia. ligand for these receptors another related member, HER4, has recently been identified by independent investigator groups called neu differentiation (NDF) or heregulin. In vitro treatment HER2- HER3- HER4-expressing breast cells stimulates phosphorylation produces changes rate proliferation, degree cellular differentiation, synthesis physiologic secretion products. There no published reports on expression NDF HER4 effects cells. METHODS Expression NDF, HER2, was studied 24 frozen prostatectomy specimens immunohistochemistry. biologic effect human recombinant vitro, using LNCaP, PC3, DU145 lines. HER mRNA analyzed reverse transcriptase polymerase chain reaction from whole RNA. included thymidine synthesis, induction prostate-specific antigen mRNA, anchorage-dependent anchorage-independent growth, ploidy analysis. Data analysis performed Student's t test. RESULTS Observations specimens: Immunohistochemistry studies demonstrate absence significant cancer, whereas it expressed 100% stroma, basal epithelial cells, 58% luminal normal benign hyperplastic tissue. strongly but not cancer. Benign tissue exhibits strong only significantly express HER4. Only 23% while 95% HER3 82% HER2. Prostatic neoplasia stained similarly to all proteins studied. lines: reduces aneuploidy proliferation androgen-sensitive Incubation also induces spite displaying do produce detectable protein, proteins. DISCUSSION These data suggest may be paracrine involved adult physiology functional loss NDF/HER ligand/ loop an early event associated tumorigenesis.