Sex steroid hormone metabolism and prostate cancer

Soronen, Pia; Laiti, M; Törn, Svea; Härkönen, Pirjo; Patrikainen, Lila; Li, Y; Pulkka, Anitta E.; Kurkela, Riitta; Herrala, Annakaisa; Kaija, Helena; Isomaa, Veli; Vihko, Pirkko

doi:10.1016/j.jsbmb.2004.10.004

Cited by 77 publications

(52 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was also reported that the AR antagonist, Casodex, inhibited DHEA-induced proliferation of LNCaP cells (Arnold et al 2007). Interactions among androgens, estrogens, and their receptors contribute to normal prostate development and function (Prins et al 1998, Risbridger et al 2003, Ho 2004, Soronen et al 2004, and to dysregulation of prostate growth, potentially promoting hormone-independent PCa (Arnold & Isaacs 2002, Heinlein & Chang 2004. In castrated rats, our result demonstrated that DHEA treatment had no significant effect in body weight.…”

Section: Discussionsupporting

confidence: 49%

Dehydroepiandrosterone-induced proliferation of prostatic epithelial cell is mediated by NFKB via PI3K/AKT signaling pathway

Sun¹,

Yang²,

Zang³

et al. 2009

Journal of Endocrinology

View full text Add to dashboard Cite

Dehydroepiandrosterone (DHEA) is an endogenous steroid that is metabolized to androgens and/or estrogens in the human prostate. DHEA levels decline with age, and use of DHEA supplements to retard the aging process is of unproved effectiveness and safety. In this study, rat ventral prostatic epithelial cells were used to determine whether DHEAmodulated proliferation and prostate-specific antigen (PSA listed as KLKB1 in the MGI Database) production were mediated via the androgen receptor (AR) and its potential mechanism. We demonstrated that proliferation of prostatic epithelial cells and increase of PSA expression induced by DHEA were neutralized by Casodex or Ar siRNA, two specific AR blockers. DHEA stimulated Nfkb DNA binding activity, with this effect being blunted by Casodex or Ar siRNA. Moreover, the inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT nullified the effects of DHEA on NFKB activation. These findings suggested that DHEA stimulated normal prostatic epithelial cell proliferation, and AR is involved in DHEA-induced PSA expression in normal prostatic epithelial cells. This stimulation effect induced by DHEA is mediated by the activation of NFKB via PI3K/AKT pathway.

show abstract

Section: Discussionsupporting

confidence: 49%

Dehydroepiandrosterone-induced proliferation of prostatic epithelial cell is mediated by NFKB via PI3K/AKT signaling pathway

Sun¹,

Yang²,

Zang³

et al. 2009

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…At present, nine different 17-HSD isoenzymes, namely types 1, 3, 5, 7 (reductive enzymes), 2, 4, 8, 10 and 11 (oxidative enzymes) have been characterized in humans. 12 In the prostate, androstenedione is converted to testosterone by 17-HSD type 5 enzyme. 12,13 In prostate cancer specimens, a reduced expression of 17-HSD type 2 mRNA has been detected 14 and the expression levels of the 17-HSD type 3 gene were significantly higher than those in nonmalignant tissues.…”

Section: Discussionmentioning

confidence: 99%

“…12 In the prostate, androstenedione is converted to testosterone by 17-HSD type 5 enzyme. 12,13 In prostate cancer specimens, a reduced expression of 17-HSD type 2 mRNA has been detected 14 and the expression levels of the 17-HSD type 3 gene were significantly higher than those in nonmalignant tissues. 15 For 5-R, it is now clear that not only 5-R type 1 but also the type 2 isozymes are expressed in the human prostate and the inhibition of both is more effective in lowering DHT than the inhibition of a single isozyme.…”

Section: Discussionmentioning

confidence: 99%

Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer

Suzuki

Nishiyama

Hara

et al. 2007

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

The metabolic pathways of androgens and processes by which androgens induce re-growth after androgen deprivation therapy in prostate cancer have not been fully elucidated. In this study, finasteride decreased PSA secretion in medium containing testosterone, androstenedione, androstenediol and dehydroepiandrosterone, whereas dihydrotestosterone (DHT)-and hydroxyflutamide-induced PSA production was not inhibited by finasteride in LNCaP-FGC cells. The present data show that adrenal androgen precursors do not directly interact with androgen receptors (ARs) but are converted to DHT via the intraprostatic metabolic pathways, resulting in the induction of LNCaP activity. This is the first report confirming this mechanism experimentally and also suggest the use of combined therapies that target ARs and prevent the formation of DHT within prostate cancer cells to achieve optimal therapeutic efficacy.

show abstract

“…A human study also reported that longterm exposure to high levels of androgens is associated with prostate cancer risk (27). Levels of testosterone, a principle circulating androgen, have further been shown to play a pivotal role in the differentiation and maintenance of selected prostate cancer cells lines both in vitro and in vivo (28).…”

Section: Possible Mechanisms: Clock-controlled Androgen Expression?mentioning

confidence: 98%

Does “Clock” Matter in Prostate Cancer?

Zhu

Zheng

Stevens

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

The ancient adaptation of a 24-hour circadian clock has profound effect on our daily biochemical, physiologic, and behavioral processes, including the monitoring of sex hormone levels. Although the disruption of the circadian cycle has been implicated in the etiology of hormone-related female breast cancer, few studies have been undertaken to determine if a link exists in the development of the most common cancer type among men whose etiology remains largely unknown: hormone-related prostate cancer. Here, we hypothesize that both altered-lighted environments and genetic variations in genes responsible for maintaining circadian rhythms may result in deregulation of clock-associated biological processes, such as androgen expression, and consequently influence an individual's risk of prostate cancer. There is also a potential for the interaction of genetic variants and exposures, such as evening shift work. Confirmation of this hypothesis will add to our understanding of the role of the circadian clock in prostate tumorigenesis and further facilitate the development of novel risk and prognostic biomarkers for prostate cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(1):3 -5)

show abstract

Sex steroid hormone metabolism and prostate cancer

Cited by 77 publications

References 45 publications

Dehydroepiandrosterone-induced proliferation of prostatic epithelial cell is mediated by NFKB via PI3K/AKT signaling pathway

Dehydroepiandrosterone-induced proliferation of prostatic epithelial cell is mediated by NFKB via PI3K/AKT signaling pathway

Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer

Does “Clock” Matter in Prostate Cancer?

Contact Info

Product

Resources

About