Increased incidence of luteinizing hormone-releasing hormone receptor gene messenger RNA expression in hormone-refractory human prostate cancers.
There are few options for treating hormone-refractory prostate cancer (PC). Various studies indicate that luteinizing hormone-releasing hormone (LHRH) agonists may have a direct inhibitory effect on prostate tumors mediated by specific LHRH receptors. One study evaluated LHRH receptors in hormone-dependent PC tissue, but no data have thus far been obtained on the presence of LHRH receptors in benign prostatic hyperplasia (BPH) and especially hormone-refractory PC in patients. Thus, it is not yet clear whether LHRH receptors indicate tumor-related differentiation or even hormone-refractory dedifferentiation or are likewise associated with BPH. The aim of this study was to determine the rate of LHRH receptor mRNA expression in BPH and in primary, potentially androgen-dependent and in hormone-refractory PC with clinical progression. Multiplex reverse transcription-PCR was used to simultaneously detect the expression of mRNA for LHRH receptors and beta-actin in 48 patients with BPH, 14 with a primary, possibly hormone-dependent, prostate carcinoma (PPC), and 18 with a hormone-refractory prostate carcinoma (HRPC). Sixteen of 18 samples with HRPC showed intact RNA and expressed mRNA for LHRH receptors (100%). However, the RNA-intact PPC and BPH showed significantly lower expression of mRNA for LHRH receptors (46.2 and 55.3%, respectively; variance analysis: P = 0.0017). The significantly higher expression of mRNA for LHRH receptors in HRPC indicates that therapeutic concepts should be developed that target this site of action. In addition to possible direct effects of LHRH agonists or antagonists demonstrated previously in vitro, it seems useful to apply targeted cytotoxic LHRH analogues or monoclonal antibodies.
Straub
B
B
Department of Urology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany. straub@medizin.fu-berlin.de
Müller
M
M
Krause
H
H
Schrader
M
M
Goessl
C
C
Heicappell
R
R
Miller
K
K
D000368:Aged; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011966:Receptors, LHRH / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D011966:Receptors, LHRH