OBJECTIVE: Metastatic prostate cancer kills patients because their tumor cells fail to respond to combined androgen blockade (CAB) or respond and then relapse. To understand the molecular basis of androgen-insensitive growth of prostate tumor cells, we evaluated changes in human androgen receptor gene (hAR) mRNA levels in patients with prostate cancer treated with CAB. METHODS: The study was carried out using quantitative reverse-transcriptase polymerase chain reaction analysis. The level of hAR mRNA were compared to serum prostate-specific antigen and the mutant status of p53 in the tumor. RESULTS: hAR was expressed in 44 of 46 tumors from untreated patients, as opposed to 30 of 45 from those who had received CAB (p = 0.001). These 30 were from 8 of 9 stage D patients and from 22 of 36 patients on downsizing CAB therapy prior to radical prostatectomy. Expression was most often seen in high stages (56% of stage B vs. 89% of stage D) and high grades (52% of Gleason 3-7 vs. 92% of Gleason 8-10, p = 0.015). No tumor with a missense p53 mutation had hAR expression following CAB. Twenty-two patients following CAB were found to have undetectable serum prostate-specific antigen levels, while their tumor expressed hAR. CONCLUSIONS: hAR expression after CAB is seen preferentially in high-grade, high-stage tumors, the type of prostate carcinomas that fail to have a durable remission. Undetectable serum prostate-specific antigen from tumors that remain hAR positive may predict relapse after hormonal ablative therapy.
OBJECTIVE:Metastatic prostate cancer kills patients because their tumor cells fail to respond to combined androgen blockade (CAB) or respond and then relapse. To understand the molecular basis of androgen-insensitive growth of prostate tumor cells, we evaluated changes in humanandrogen receptor gene (hAR) mRNA levels in patients with prostate cancer treated with CAB. METHODS: The study was carried out using quantitative reverse-transcriptase polymerase chain reaction analysis. The level of hAR mRNA were compared to serum prostate-specific antigen and the mutant status of p53 in the tumor. RESULTS:hAR was expressed in 44 of 46 tumors from untreated patients, as opposed to 30 of 45 from those who had received CAB (p = 0.001). These 30 were from 8 of 9 stage D patients and from 22 of 36 patients on downsizing CAB therapy prior to radical prostatectomy. Expression was most often seen in high stages (56% of stage B vs. 89% of stage D) and high grades (52% of Gleason 3-7 vs. 92% of Gleason 8-10, p = 0.015). No tumor with a missense p53 mutation had hAR expression following CAB. Twenty-two patients following CAB were found to have undetectable serum prostate-specific antigen levels, while their tumor expressed hAR. CONCLUSIONS:hAR expression after CAB is seen preferentially in high-grade, high-stage tumors, the type of prostate carcinomas that fail to have a durable remission. Undetectable serum prostate-specific antigen from tumors that remain hAR positive may predict relapse after hormonal ablative therapy.
Authors: Rosalinda M Savoy; Liqun Chen; Salma Siddiqui; Frank U Melgoza; Blythe Durbin-Johnson; Christiana Drake; Maitreyee K Jathal; Swagata Bose; Thomas M Steele; Benjamin A Mooso; Leandro S D'Abronzo; William H Fry; Kermit L Carraway; Maria Mudryj; Paramita M Ghosh Journal: Endocr Relat Cancer Date: 2015-03-10 Impact factor: 5.678
Authors: Mark A Titus; Jiann-An Tan; Christopher W Gregory; O Harris Ford; Romesh R Subramanian; Haian Fu; Elizabeth M Wilson; James L Mohler; Frank S French Journal: Clin Cancer Res Date: 2009-12-15 Impact factor: 12.531
Authors: Shihua Wang; Jiansheng Wu; Janel Suburu; Zhennan Gu; Jiaozhong Cai; Linara S Axanova; Scott D Cramer; Michael J Thomas; Donna L Perry; Iris J Edwards; Lorelei A Mucci; Jennifer A Sinnott; Massimo F Loda; Guangchao Sui; Isabelle M Berquin; Yong Q Chen Journal: Carcinogenesis Date: 2011-12-08 Impact factor: 4.944