title: Modulation of cytokeratin subtype, EGF receptor, and androgen receptor expression during progression of prostate cancer.
abstract: After initial regression in response to androgen deprivation, most prostate cancers develop resistance to endocrine therapy. Identification of cellular and molecular changes occurring during endocrine therapy-induced regression and subsequent hormone insensitivity may point to mechanisms underlying the transition to hormone-independent prostate cancer. A series of untreated (n = 24), regressed (n = 15), and endocrine therapy-resistant (n = 10) prostatic adenocarcinomas were analyzed using immunohistochemistry with regard to cytokeratin 5 and 18, androgen receptor (AR), and epidermal growth factor receptor (EGF-R) expression in tumor cells. Using semiquantitative reverse transcription-polymerase chain reaction, the amount of AR mRNA also was determined. In regressed and therapy-resistant prostate cancers, an increase in cytokeratin 5-positive tumor cells was noted when compared with untreated carcinomas. Similarly, the proportion of EGF-R-positive tumor cells increased in the treated cases, whereas the proportion of AR-positive tumor cells dropped in regressed carcinomas and increased in hormone-refractory cancers. In the latter group, an eightfold higher level of AR mRNA was observed when compared with the other cases. Changes in the proportion of cytokeratin 5 and EGF-R-positive tumor cells suggests that during androgen deprivation an enlarged subpopulation of tumor cells with combined features of basal and secretory phenotypes arises. The increased proportion of AR-positive tumor cells during the transition from the regression phase to the hormone escape phase points to an important role of AR overexpression in this process.
authors.affiliation: Groupe d'Etude des Tumeurs Urologiques, Centre de Recherches Chirurgicales, Hopital Henri Mondor, Créteil, France.
authors.forename: S
authors.initials: S
authors.lastname: Gil-Diez de Medina
authors.forename: L
authors.initials: L
authors.lastname: Salomon
authors.forename: M
authors.initials: M
authors.lastname: Colombel
authors.forename: C C
authors.initials: CC
authors.lastname: Abbou
authors.forename: J
authors.initials: J
authors.lastname: Bellot
authors.forename: J P
authors.initials: JP
authors.lastname: Thiery
authors.forename: F
authors.initials: F
authors.lastname: Radvanyi
authors.forename: T H
authors.initials: TH
authors.lastname: Van der Kwast
authors.forename: D K
authors.initials: DK
authors.lastname: Chopin
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D011944:Receptors, Androgen; D007633:Keratins; D066246:ErbB Receptors