Type 1 and Type 2 5α-Reductase Expression in the Development and Progression of Prostate Cancer

Thomas, Lynn N.; Douglas, Robert G.; Lazier, Catherine B.; Too, Catherine K.L.; Rittmaster, Roger S.; Tindall, Donald J.

doi:10.1016/j.eururo.2007.10.052

Cited by 101 publications

(88 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although several reports have ascribed the phenomenon to bias in tissue sampling, uncertainty in the reproducibility of histological diagnosis, and increased PSA sensitivity, the main concern is the molecular profile of AR and the associated signaling pathway (25)(26)(27). In this study, 5ARI had been proven to be able to change the expression profile of AR and other oncogenic factors such as HOXB13.…”

Section: Discussionmentioning

confidence: 72%

Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

et al. 2013

View full text Add to dashboard Cite

Objectives: Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. Materials and Methods:We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. Results: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. Conclusions: These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway. Five-alpha

show abstract

Section: Discussionmentioning

confidence: 72%

Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

et al. 2013

View full text Add to dashboard Cite

show abstract

“…6 However, more recently, 5-AR1 expression has also been shown to be increased in prostate cancer compared with normal and BPH tissue at both the messenger RNA (mRNA) level 10,11 and at the protein level. 10,12 Thomas and colleagues provide a review of this data.…”

Section: -Ars and Prostate Cancer Developmentmentioning

confidence: 99%

The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme?

Goldenberg

Fleshner

et al. 2013

CUAJ

View full text Add to dashboard Cite

Normal growth and function of the prostate are contingent on the reductionof testosterone to dihydrotestosterone (DHT) by 5-alpha reductase(5-AR) enzymes types 1 and 2. It has been theorized that an overabundanceof DHT may be implicated in the pathogenesis of both benign prostatic hyperplasia(BPH) and prostate cancer. Inhibitors of 5-AR such as dutasteride andfinasteride may therefore have an important role in the prevention and treatmentof BPH and prostate cancer. Dutasteride provides greater suppression ofDHT than finasteride, thereby underlying the hypothesis that inhibition of bothtype 1 and type 2 would provide correspondingly greater protection than inhibitionof type 2 alone. We review the potential significance of the 5-ARinhibitors in reducing the risk of prostate cancer according to the basic biologyof prostate disease

show abstract

“…Compared with testosterone, DHT has a greater binding affinity for the androgen receptor and results in 2-to 10-fold greater translational activity. 10 Finasteride-induced reductions in DHT concentrations result in decreased activation of the androgen receptor, decreased prostate volume, and increased prostatic cell apoptosis. 11 In the PCPT, 18 882 men were randomized to receive either finasteride or placebo over a 9-year period.…”

Section: Primary Preventionmentioning

confidence: 99%

“…Although type 2 is the predominant form in the prostate, type 1 potentially has a more substantial function in the development of prostate cancer than was earlier thought. 10,[33][34][35] As dutasteride inhibits both isoforms, it results in greater reductions in serum and intraprostatic DHT levels than finasteride. [36][37][38][39] REDUCE was a 4-year, multi-institutional, RCT of 0.5 mg daily oral dutasteride versus placebo in 8000 men.…”

Section: Primary Preventionmentioning

confidence: 99%

Prostate cancer prevention: concepts and clinical recommendations

Silberstein

Parsons

2010

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

Prevention is an important strategy for limiting prostate cancer morbidity and mortality. Two major types of prevention are primary (reduction of incident cases) and tertiary (inhibition of disease progression and recurrence). Pharmacological and dietary interventions have potential functions in both the primary and tertiary prevention of prostate cancer. Five-a reductase inhibitors (5-ARIs) reduce the incidence of prostate cancer in both general and higher-risk populations and are currently under study for tertiary prevention in active surveillance and biochemical recurrence patients. Selenium, vitamin E, and vitamin C do not prevent incident prostate cancer in the general population; however, other promising diet-based interventions are currently under study for tertiary prevention. We recommend consideration of 5-ARIs for prostate cancer prevention in (1) asymptomatic men with a PSA p3.0 ng ml -1 who are undergoing or anticipate undergoing PSA screening for early detection of prostate cancer and (2) asymptomatic men with PSA X2.5 and p10 ng ml -1 and an earlier prostate biopsy negative for cancer. Men should be informed of the potential risks of 5-ARI therapy. Currently, there is neither clinical evidence to support the use of 5-ARIs for tertiary prevention in active surveillance or biochemical recurrence populations, nor micronutrients for prostate cancer prevention of any type.

show abstract

Type 1 and Type 2 5α-Reductase Expression in the Development and Progression of Prostate Cancer

Cited by 101 publications

References 47 publications

Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme?

Prostate cancer prevention: concepts and clinical recommendations

Contact Info

Product

Resources

About