Apoptosis and hormonal milieu in ductal system of normal prostate and benign prostatic hyperplasia

Aim: To study the apoptotic rate (AR) and the androgen and estrogen milieu in the proximal and distal ductal sys-tems of prostate, in order to help exploring the effects of these factors on prostatic growth and the pathogenesis of be-nign prostatic hypertrophy (BPH). Methods: The proximal and distal ends of the ductal system were incised from20 normal prostate as well as the hypertrophic prostate tissue from 20 patients with BPH. The AR was determined bythe DNA end-labeling method and dihydrotestosterone (DHT) and estrodiol (E_2), by radioimmunoassay. Results:There was no significant difference in DHT and E_2 density between the proximal and distal ends of the ductal systems innormal prostate. E_2 appeared to be higher in BPH than in normal prostatic tissues, but the difference was statistically in-significant. In normal prostatic tissue, the AR was significantly higher in the distal than in the proximal ends of theductal system (P<0.05), while the AR of the proximal ends was significantly higher (P <0.01) than that in theBPH tissue. No significant correlation was noted between the DHT and E_2 density and the AR both in the normalprostate and BPH tissues. Conclusion: The paper is the first time describing a difference in AR in different regionsof the ductal system of normal prostate, while the hormonal milieu is similar, indicating a functional inhomogeneity ofthese regions. A low AR in the proximal duct, where BPH originates, and an even lower AR in the BPH tissue, sug-gesting the participation of apoptosis in the BPH pathogenesis.

Androgen receptor isoforms in human prostatic cancer tissue and LNCaP cell line

Aim: To investigate the androgen receptor (AR) isoform expressions in human prostatic cancer tissue and LNCaPcell line. Methods: With high resolution isoelectric focusing (IEF) method we demonstrated the different expres-sions of AR isoforms in human prostatic cancer tissues and LNCaP cell line. Results; Data were obtained from threeprostatic cancer specimens and the LNCaP cell line. Three types of AR isoforms were detected with pI values at 6.5,6.0, and 5.3. For the 3 prostatic cancer specimens, 1 sample showed all the three types of AR isoforms, the secondspecimen expressed at 6.5 and 6.0, and the third failed to show any type of isoforms. The LNCaP cell line expressedall the three AR isoforms. Binding of ~3H-dihydrotestosterone (~3H-DHT) to these three isoforms was inhibited by the ad-dition of 100-fold excess of DHT or testosterone, while not by progesterone, oestradiol and diethylstilboestrol. Conclu-sion : The expression of AR isoforms is different in different prostate cancer tissues, which may be related to the dif-ference in the effect of anti-androgen therapy in different patients. (Asian J Androl 2001 Sep; 3: 223 - 225)

Androgen receptor isoforms in human and rat prostate

Aim: To investigate the androgen receptor (AR) isoforms and its variability of expression in human and rat prostatictissues. Methods: Human benign prostatic hyperplasia (BPH) and prostatic cancer tissues were obtained from pa-tients undergoing prostatectomy, and rat ventral prostate was incised 3 days after castration. Forty-one AR-positive BPHspecimens, 3 prostatic cancer specimens, and 6 rat prostates were used. After processing at 4℃, the tissues were ex-amined by means of high resolution isoelectric focusing (IEF) technique to determine their AR isoforms. Results:From the prostatic specimens, 3 types of AR isoforms were detected with pI values at 6.5, 6.0, and 5.3. In humanBPH tissues, 15/41 (36.6%) specimens showed all the three types of isoforms, while 19/41 (46.3%) showed 2 iso-fora at various combinations and 7/41 (17.1%), 1 isoform. For the 3 prostatic cancer specimens, one showed 3 iso-forms, one, 2 isoforms, and the other failed to show any isoform. All rat prostatic tissues showed 2 isoforms at differ-ent combinations. Binding of ~3H-dihydrotestosterone (DHT) to the isoforms was inhibited by the addition of 100-foldexcess of DHT or testosterone, but not progesterone, oestradiol or diethylstilboestrol. Conclusion: AR isoforms aredifferent in different patients. Although their genesis is not clear, the therapeutic implication of the present observationappears to be interesting, that may help clarifying the individual differences in the response to hormonal therapy.(Asian J Androl 2000 Dec; 2: 307-310)

Radiation and androgen withdrawal alter expression of apoptosis pathway genes of prostate cancer cells

Aim: To investigate the altered expression of apoptosis pathway genes of prostate cancer cells treated by radiation and androgen withdrawal and whether the combined treatment may induce additive apoptosis. Methods: Androgen sensitive prostate cancer cell line LNCaP was cultured and treated by radiation, androgen withdrawal and combination of the two. Apoptosis was determined using apoptotic cells staining and mononuclear cell direct cytotox-icity assay. The total RNA were extracted and harvested. cDNA probes were prepared and labeled with biotin-16-dUTP and then hybridized to commercially available cDNA arrays, including apoptosis pathway-specific genes. The expression of important gene was further determined using RT-PCR. Results: Radiation induced additive apoptosis of prostate cancer cells; androgen withdrawal exhibited synergetic action. TNFRSF8 variant 2, DFFA, LTbR, mdm2, Myd88, TNFRSF14 and TNFSF4 mRNA were up regulated by radiation, while Survivin and Bar mRNA were down regulated. Mcl-1, TNFRSF14, MyD88 and TNFSF4 mRNA were up regulated by androgen withdrawal, while Bar, Survivin and TRAIL-R3 mRNA were down regulated. Conclusion: Radiation and androgen withdrawal altered the expression of apoptosis pathway genes of prostate cancer cells in different patterns, which may contribute to the additive apoptotic effect induced by the combined treatment.