Induction of NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase Expression by Androgens in Human Prostate Cancer Cells

Tang, Min; Tai, Hsin‐Hsiung

doi:10.1006/bbrc.2000.3437

Cited by 44 publications

(19 citation statements)

References 27 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PGE 2 excretion was found higher in females than in males. As already described in human (25), differential production of PGE 2 in male and female rats and mice had generally been ascribed to enhanced COX-2 and decreased NADdependent 15-PGDH (26,27). However, as in human hair follicle COX-1 is constitutive and COX-2 barely expressed (13), our present results rather argue for a key role of mPGES and AKR1C3 ⁄ PGFS downstream COX-1 in prostaglandin pathway.…”

Section: Discussionsupporting

confidence: 78%

Prostaglandin metabolism in human hair follicle

Colombe

Vindrios

Michelet

et al. 2007

Experimental Dermatology

View full text Add to dashboard Cite

Prostaglandins regulate a wide number of physiological functions. Recently PGF 2a analogue such as latanoprost was shown to have a real impact on hair regrowth. The aim of this study was to investigate and describe the expression profile in human hair follicle of prostaglandin metabolism key enzymes, i.e. carbonyl reductase-1 (CBR1), microsomal prostaglandin E synthase-1 (mPGES-1) and microsomal prostaglandin E synthase-2 (mPGES-2), cytosolic prostaglandin E synthase (cPGES), the aldoketoreductase AKR1C1 and the prostaglandin F synthase AKR1C3. Quantitative RT-PCR on plucked hair follicles revealed some sex-related differences, mPGES-2 and AKR1C3 expression levels being higher in women. Cell and hair follicle compartment specificity was investigated using Western blot, PGE 2 and PGF 2a ELISA assays and immunohistochemistry. Most of the hair cell types were endowed with prostaglandin metabolism machinery and were thus able to produce PGE 2 and ⁄ or PGF 2a . The epithelial part of the hair bulb was identified by immunohistology and EIA assays as the main source of prostaglandin synthesis and interconversion. All these observations support the concept that prostaglandins might be involved in hair growth and differentiation control.

show abstract

Section: Discussionsupporting

confidence: 78%

Prostaglandin metabolism in human hair follicle

Colombe

Vindrios

Michelet

et al. 2007

Experimental Dermatology

View full text Add to dashboard Cite

show abstract

“…15-PGDH is widely expressed in many mammalian tissues (38) and has been shown to be modulated by several hormones and factors (37)(38)(39), indicating the potential importance of the regulation of this enzyme. In LNCaP cells, 15-PGDH expression is up-regulated by androgens, interleukin-6, and the cyclic AMP inducer forskolin in a protein kinase A-dependent manner (40,41). We now show that calcitriol is an important regulator of 15-PGDH expression in prostate cancer cells.…”

Section: Discussionmentioning

confidence: 57%

Regulation of Prostaglandin Metabolism by Calcitriol Attenuates Growth Stimulation in Prostate Cancer Cells

et al. 2005

View full text Add to dashboard Cite

Calcitriol exhibits antiproliferative and prodifferentiation effects in prostate cancer. Our goal is to further define the mechanisms underlying these actions. We studied established human prostate cancer cell lines and primary prostatic epithelial cells and showed that calcitriol regulated the expression of genes involved in the metabolism of prostaglandins (PGs), known stimulators of prostate cell growth. Calcitriol significantly repressed the mRNA and protein expression of prostaglandin endoperoxide synthase/cyclooxygenase-2 (COX-2), the key PG synthesis enzyme. Calcitriol also up-regulated the expression of 15-hydroxyprostaglandin dehydrogenase, the enzyme initiating PG catabolism. This dual action was associated with decreased prostaglandin E 2 secretion into the conditioned media of prostate cancer cells exposed to calcitriol. Calcitriol also repressed the mRNA expression of the PG receptors EP2 and FP, providing a potential additional mechanism of suppression of the biological activity of PGs. Calcitriol treatment attenuated PG-mediated functional responses, including the stimulation of prostate cancer cell growth. The combination of calcitriol with nonsteroidal antiinflammatory drugs (NSAIDs) synergistically acted to achieve significant prostate cancer cell growth inhibition at f2 to 10 times lower concentrations of the drugs than when used alone. In conclusion, the regulation of PG metabolism and biological actions constitutes a novel pathway of calcitriol action that may contribute to its antiproliferative effects in prostate cells. We propose that a combination of calcitriol and nonselective NSAIDs might be a useful chemopreventive and/or therapeutic strategy in men with prostate cancer, as it would allow the use of lower concentrations of both drugs, thereby reducing their toxic side effects. (Cancer Res 2005; 65(17): 7917-25)

show abstract

“…To test this model further, we used a cell type that expresses endogenous PG15DH. In the human prostate cancer cell line LNCaP, PG15DH activity is induced by DHT (Tong and Tai, 2000). We transiently transfected LNCaP cells with rPGT, added PGE2, and assayed for the appearance of the metabolite 13,14-dihydro,15-keto-PGE2 and for cellular PGE2 retention.…”

Section: Resultsmentioning

confidence: 99%

“…The human prostate cell line LNCaP was obtained from American Type Culture Collection and grown with dihydrotestosterone (DHT) as described previously (Tong and Tai, 2000). For expression of PGT, cells were incubated with the transfection complexes for 48 h. Before uptake assays, they were preincubated with 100 M ASA for 2 h. Thereafter, the uptake of PGE2, the extraction of PGE2, and the appearance of 13,14-dihydro,15-keto-PGE2 were assayed as described above.…”

Section: Methodsmentioning

confidence: 99%

The Two-Step Model of Prostaglandin Signal Termination: In Vitro Reconstitution with the Prostaglandin Transporter and Prostaglandin 15 Dehydrogenase

et al. 2004

View full text Add to dashboard Cite

Termination of prostaglandin (PG) signaling has been proposed to involve carrier-mediated uptake across the plasma membrane followed by cytoplasmic oxidation. Here, we tested this hypothesis directly by coexpressing the PG uptake carrier prostaglandin transporter (PGT) in various cell types with and without human PG 15 dehydrogenase (PG15DH). In HeLa cells, which express neither PGT nor PG15DH, exogenously added PGE2 or PGF2␣ were rapidly oxidized to the 13,14-dihydro,15-keto metabolites only when PGT and PG15DH were coexpressed, directly confirming the two-step hypothesis. Cells expressing PG15DH that were broken open formed more PG metabolites than cells in which the PGs could gain access to PG15DH only via PGT. Similar results were obtained using the human prostate cancer cell line LNCaP, in which endogenous PG15DH is induced after exposure to dihydrotestosterone. Because PGT in vivo is expressed in renal collecting duct epithelia, we also expressed PGT in Madin-Darby canine kidney cells grown on filters, where it mediated both the active uptake of PGE2 across the apical membrane and the transepithelial transport of PGE2 to the basolateral compartment. When PG15DH was coexpressed with PGT in these epithelial monolayers, about half of the PGE2 taken up apically was oxidized to 13,14-dihydro,15-keto-PGE2, which in turn exited the cells nondirectionally into both the apical and basolateral compartments. Our data represent reconstitution of the longstanding model of PG metabolism consisting of sequential carrier-mediated PG uptake, cytoplasmic oxidation, and diffusional efflux of the PG metabolite.

show abstract

Induction of NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase Expression by Androgens in Human Prostate Cancer Cells

Cited by 44 publications

References 27 publications

Prostaglandin metabolism in human hair follicle

Prostaglandin metabolism in human hair follicle

Regulation of Prostaglandin Metabolism by Calcitriol Attenuates Growth Stimulation in Prostate Cancer Cells

The Two-Step Model of Prostaglandin Signal Termination: In Vitro Reconstitution with the Prostaglandin Transporter and Prostaglandin 15 Dehydrogenase

Contact Info

Product

Resources

About