Background: Prostate cancer is initially dependent on androgens for survival and growth, making hormonal therapy the cornerstone treatment for late-stage tumors. However, despite initial remission, the cancer will inevitably recur. The present study was designed to investigate how androgen-dependent prostate cancer cells eventually survive and resume growth under androgen-deprived and antiandrogen supplemented conditions. As model system, we used the androgen-responsive PC346C cell line and its therapy-resistant sublines: PC346DCC, PC346Flu1 and PC346Flu2.
Methodology/principal Findings: Microarray technology was used to analyze differences in gene expression between the androgen-responsive and therapy-resistant PC346 cell lines. Microarray analysis revealed 487 transcripts differentially-expressed between the androgen-responsive and the therapy-resistant cell lines. Most of these genes were common to all three therapy-resistant sublines and only a minority (∼5%) was androgen-regulated. Pathway analysis revealed enrichment in functions involving cellular movement, cell growth and cell death, as well as association with cancer and reproductive system disease. PC346DCC expressed residual levels of androgen receptor (AR) and showed significant down-regulation of androgen-regulated genes (p-value = 10(-7)). Up-regulation of VAV3 and TWIST1 oncogenes and repression of the DKK3 tumor-suppressor was observed in PC346DCC, suggesting a potential AR bypass mechanism. Subsequent validation of these three genes in patient samples confirmed that expression was deregulated during prostate cancer progression.
Conclusions/significance: Therapy-resistant growth may result from adaptations in the AR pathway, but androgen-independence may also be achieved by alternative survival mechanisms. Here we identified TWIST1, VAV3 and DKK3 as potential players in the bypassing of the AR pathway, making them good candidates as biomarkers and novel therapeutical targets.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957443 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0013500 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Cancer statistics, 2025.
CA Cancer J Clin
January 2025
Surveillance and Health Equity Science, American Cancer Society, Atlanta, Georgia, USA.
Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2021) and mortality data collected by the National Center for Health Statistics (through 2022). In 2025, 2,041,910 new cancer cases and 618,120 cancer deaths are projected to occur in the United States. The cancer mortality rate continued to decline through 2022, averting nearly 4.
View Article and Find Full Text PDFA new parameter to increase the predictive value of multiparametric prostate magnetic resonance imaging for clinically significant prostate cancer in targeted biopsies: lesion density.
Prostate Int
September 2024
Gazi University School of Medicine, Urology Department, Ankara, Turkey.
Aim: To investigate the predictive value of lesion length in multiparametric prostate magnetic resonance imaging with respect to prostate volume for clinically significant prostate cancer diagnosis in targeted biopsies.
Materials And Methods: The data of biopsy-naïve patients in the Turkish Urooncology Association Prostate Cancer Database who underwent targeted prostate biopsies were included in this study. Lesion density is calculated as the ratio of lesion length (mm) in MR to prostate volume (cc).
Comparison of oncological outcomes between extended and no pelvic lymph node dissection in patients with high- or very high-risk prostate cancer: a multi-institutional study.
Prostate Int
September 2024
Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Japan.
Background: Despite providing valuable staging and prognostic information, the therapeutic benefit of pelvic lymph node dissection (PLND) remains uncertain. We sought to assess the effect of extended PLND (ePLND) on the biochemical recurrence (BCR) of patients with National Comprehensive Cancer Net (NCCN) high- or very high-risk prostate cancer treated via robot-assisted radical prostatectomy (RARP).
Methods: We used a multi-institutional database (six centers) to assess 989 patients who underwent RARP from 2014 to 2022 with or without ePLND, among which 699 patients underwent BCR analysis.
Hematospermia does not increase the risk of prostate cancer detection in prostate biopsy.
Prostate Int
September 2024
Department of Urology, Konkuk University Medical Center, Seoul, Korea.
Background: Studies on the association between hematospermia and prostate cancer are insufficient. The purpose of this study was to determine the prevalence of prostate cancer in patients with hematospermia using large United States population data.
Materials And Methods: This was a retrospective observational cohort study.
Does the type of the previous biopsy affect the fusion prostate biopsy results?
Prostate Int
September 2024
Erciyes University, Department of Urology, Devision of UroOncology, Kayseri, Turkey.
Background: It has been more than a decade since fusion prostate biopsy (FPB) has been used in the diagnosis of prostate cancer (PCa). Therefore, patients with a previous history of negative FPB and ongoing suspicion of PCa are beginning to emerge. This study investigated whether the first biopsy type (standard or fusion) should be effective in deciding on a second biopsy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!