scholarly journals Induction of 3β-Hydroxysteroid Dehydrogenase/ Isomerase Type 1 Expression by Interleukin-4 in Human Normal Prostate Epithelial Cells, Immortalized Keratinocytes, Colon, and Cervix Cancer Cell Lines1

Endocrinology ◽  
1999 ◽  
Vol 140 (10) ◽  
pp. 4573-4584 ◽  
Author(s):  
Sébastien Gingras ◽  
Jacques Simard
Keyword(s):  
Epithelial Cells ◽  
Cancer Cell ◽  
Hydroxysteroid Dehydrogenase ◽  
Cervix Cancer ◽  
Interleukin 4 ◽  
Normal Prostate ◽  
Prostate Epithelial Cells

scholarly journals Increased expression of type 2 3α-hydroxysteroid dehydrogenase/type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma

2006 ◽  
Vol 13 (1) ◽  
pp. 169-180 ◽  
Author(s):  
K-M Fung ◽  
E N S Samara ◽  
C Wong ◽  
A Metwalli ◽  
R Krlin ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Androgen Receptor ◽  
Epithelial Cells ◽  
Prostate Carcinoma ◽  
Primary Cultures ◽  
Hydroxysteroid Dehydrogenase ◽  
Human Prostate ◽  
Normal Prostate ◽  
Prostate Epithelial Cells

Type 2 3α-hydroxysteroid dehydrogenase (3α-HSD) is a multi-functional enzyme that possesses 3α-, 17β- and 20α-HSD, as well as prostaglandin (PG) F synthase activities and catalyzes androgen, estrogen, progestin and PG metabolism. Type 2 3α-HSD was cloned from human prostate, is a member of the aldo-keto reductase (AKR) superfamily and was named AKR1C3. In androgen target tissues such as the prostate, AKR1C3 catalyzes the conversion of Δ4-androstene-3,17-dione to testosterone, 5α-dihydrotestosterone to 5α-androstane-3α,17β-diol (3α-diol), and 3α-diol to androsterone. Thus AKR1C3 may regulate the balance of androgens and hence trans-activation of the androgen receptor in these tissues. Tissue distribution studies indicate that AKR1C3 transcripts are highly expressed in human prostate. To measure AKR1C3 protein expression and its distribution in the prostate, we raised a monoclonal antibody specifically recognizing AKR1C3. This antibody allowed us to distinguish AKR1C3 from other AKR1C family members in human tissues. Immunoblot analysis showed that this monoclonal antibody binds to one species of protein in primary cultures of prostate epithelial cells and in LNCaP prostate cancer cells. Immunohistochemistry with this antibody on human prostate detected strong nuclear immunoreactivity in normal stromal and smooth muscle cells, perineurial cells, urothelial (transitional) cells, and endothelial cells. Normal prostate epithelial cells were only faintly immunoreactive or negative. Positive immunoreactivity was demonstrated in primary prostatic adenocarcinoma in 9 of 11 cases. Variable increases in immunoreactivity for AKR1C3 was also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy and urothelial (transitional) cell metaplasia. We conclude that elevated expression of AKR1C3 is highly associated with prostate carcinoma. Although the biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain, AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on prostatic epithelial cells.

scholarly journals Proteolytic cleavage and truncation of NDRG1 in human prostate cancer cells, but not normal prostate epithelial cells

2013 ◽  
Vol 33 (3) ◽  
Author(s):  
Mohammad K. Ghalayini ◽  
Qihan Dong ◽  
Des R. Richardson ◽  
Stephen J. Assinder
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Western Blot ◽  
Cancer Cells ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Metastasis Suppressor ◽  
Normal Prostate ◽  
Truncated Protein ◽  
Prostate Epithelial Cells

NDRG1 (N-myc downstream regulated gene-1) is a metastasis suppressor that is down-regulated in prostate cancer. NDRG1 phosphorylation is associated with inhibition of metastasis and Western blots indicate two bands at ~41 and ~46 kDa. Previous investigations by others suggest the higher band is due to NDRG1 phosphorylation. However, the current study using a dephosphorylation assay and the Phos-tag (phosphate-binding tag) SDS/PAGE assay, demonstrated that the 46 kDa NDRG1 protein band was not due to phosphorylation. Further experiments showed that the NDRG1 protein bands were not affected upon glycosidase treatment, despite marked effects of these enzymes on the glycosylated protein, fetuin. Analysis using RT–PCR (reverse transcriptase–PCR) demonstrated only a single amplicon, and thus, the two bands could not result from an alternatively spliced NDRG1 transcript. Western-blot analysis of prostate cancer cell lysates identified the 41 kDa band to be a truncated form of NDRG1, with MS confirming the full and truncated proteins to be NDRG1. Significantly, this truncated protein was not present in normal human PrECs (prostate epithelial cells). Western-blot analysis using anti-NDRG1 raised to its N-terminal sequence failed to detect the truncated protein, suggesting that it lacked N-terminus amino acids (residues 1–49). Sequence analysis predicted a pseudotrypsin protease cleavage site between Cys49–Gly50. Such cleavage of NDRG1 in cancer cells may result in loss of NDRG1 tumour suppressive activity.

Prostate epithelial cell differentiation and its relevance to the understanding of prostate cancer therapies

2004 ◽  
Vol 108 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Ronan M. LONG ◽  
Colm MORRISSEY ◽  
John M. FITZPATRICK ◽  
R. William G. WATSON
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Prostate Gland ◽  
Western World ◽  
Cancer Therapies ◽  
Normal Prostate ◽  
Full Characterization ◽  
Prostate Epithelial Cells ◽  
Common Malignancy

Prostate cancer is the most common malignancy in males in the western world. However, little is known about its origin and development. This review highlights the biology of the normal prostate gland and the differentiation of basal epithelial cells to a secretory phenotype. Alterations in this differentiation process leading to cancer and androgen-independent disease are discussed, as well as a full characterization of prostate epithelial cells. A full understanding of the origin and characteristics of prostate cancer epithelial cells will be important if we are to develop therapeutic strategies to combat the heterogeneous nature of this disease.

scholarly journals Caspase- and Serine Protease-dependent Apoptosis by the Death Domain of FADD in Normal Epithelial Cells

2003 ◽  
Vol 14 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Jacqueline Thorburn ◽  
Laura M. Bender ◽  
Michael J. Morgan ◽  
Andrew Thorburn
Keyword(s):  
Epithelial Cells ◽  
Serine Protease ◽  
Death Domain ◽  
Cell Type ◽  
Normal Prostate ◽  
Effector Domain ◽  
Death Effector Domain ◽  
Prostate Epithelial Cells ◽  
Cell Type Specific ◽  
Death Effector

The adapter protein FADD consists of two protein interaction domains: a death domain and a death effector domain. The death domain binds to activated death receptors such as Fas, whereas the death effector domain binds to procaspase 8. An FADD mutant, which consists of only the death domain (FADD-DD), inhibits death receptor–induced apoptosis. FADD-DD can also activate a mechanistically distinct, cell type–specific apoptotic pathway that kills normal but not cancerous prostate epithelial cells. Here, we show that this apoptosis occurs through activation of caspases 9, 3, 6, and 7 and a serine protease. Simultaneous inhibition of caspases and serine proteases prevents FADD-DD–induced death. Inhibition of either pathway alone does not prevent cell death but does affect the morphology of the dying cells. Normal prostate epithelial cells require both the caspase and serine protease inhibitors to efficiently prevent apoptosis in response to TRAIL. In contrast, the serine protease inhibitor does not affect TRAIL-induced death in prostate tumor cells suggesting that the FADD-DD–dependent pathway can be activated by TRAIL. This apoptosis pathway is activated in a cell type–specific manner that is defective in cancer cells, suggesting that this pathway may be targeted during cancer development.

scholarly journals 17β-Hydroxysteroid Dehydrogenase Type 1 and 2 Expression in the Human Fetus1

2000 ◽  
Vol 85 (1) ◽  
pp. 410-416 ◽  
Author(s):  
Junji Takeyama ◽  
Takashi Suzuki ◽  
Gen Hirasawa ◽  
Yasunari Muramatsu ◽  
Hiroshi Nagura ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Epithelial Cells ◽  
Ribonucleic Acid ◽  
Estrogenic Activity ◽  
Expression Patterns ◽  
Hydroxysteroid Dehydrogenase ◽  
Pcr Analysis ◽  
Maternal Circulation ◽  
Messenger Ribonucleic Acid

The present study investigates the expression patterns of 17β-hydroxysteroid dehydrogenase (17βHSD) isozymes in human fetal tissues to understand how estrogenic activity is regulated in the human fetus. Using enzyme assay, high 17βHSD activity was detected in the placenta and liver, and low levels of 17βHSD activity were also present in the gastrointestinal tract and kidney. After Northern blot analysis, we detected the messenger ribonucleic acid for 17βHSD type 1 (17βHSD1) only in the placenta, whereas that for 17βHSD type 2 (17βHSD2) was detected in the placenta, liver, gastrointestinal tract, and urinary tract at 20 gestational weeks. In RT-PCR analysis of the messenger ribonucleic acid transcripts, 17βHSD1 was predominantly expressed in the placenta, brain, heart, lung, and adrenal, whereas 17βHSD2 expression was predominantly detected in the liver, gastrointestinal tract, and kidney. In addition, we detected 17βHSD2 immunoreactive protein in surface epithelial cells of the stomach, absorptive epithelial cells of the small intestine and colon, hepatocytes of the liver, and interstitial cells surrounding the urinary tubules of the renal medulla. 17βHSD2 in these tissues may be functioning in the prevention of in utero exposure of the fetus to excessive estradiol from the maternal circulation and amniotic fluids.

scholarly journals Proliferative responses to altered 17β-hydroxysteroid dehydrogenase (17HSD) type 2 expression in human breast cancer cells are dependent on endogenous expression of 17HSD type 1 and the oestradiol receptors

2006 ◽  
Vol 13 (3) ◽  
pp. 875-884 ◽  
Author(s):  
A Jansson ◽  
C Gunnarsson ◽  
O Stål
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Hydroxysteroid Dehydrogenase ◽  
S Phase ◽  
Phase Fraction ◽  
Mcf7 Cells ◽  
Endogenous Expression

The primary source of oestrogen in premenopausal women is the ovary but, after menopause, oestrogen biosynthesis in peripheral tissue is the exclusive site of formation. An enzyme group that affects the availability of active oestrogens is the 17β-hydroxysteroid dehydrogenase (17HSD) family. In breast cancer, 17HSD type 1 and type 2 have been mostly investigated and seem to be the principal 17HSD enzymes involved thus far. The question whether 17HSD type 1 or type 2 is of greatest importance in breast tumour development is still not clear. The aim of this study was to investigate how the loss of 17HSD type 2 expression, using siRNA in the non-tumour breast epithelial cells HMEC (human mammal epithelial cells) and MCF10A, and gain of 17HSD type 2 expression, using transient transfection in the breast cancer derived cell lines MCF7 and T47D, affect oestradiol conversion and proliferation rate measured as S-phase fraction. We further investigated how this was related to the endogenous expression of 17HSD type 1 and oestradiol receptors in the examined cell lines. The oestradiol level in the medium changed significantly in the MCF7 transfected cells and the siRNA-treated HMEC cells, but not in T47D or MCF10A. The S-phase fraction decreased in the 17HSD type 2-transfected MCF7 cells and the siRNA-treated HMEC cells. The results seemed to be dependent on the endogenous expression of 17HSD type 1 and the oestradiol receptors. In conclusion, we found that high or low levels of 17HSD type 2 affected the oestradiol concentration significantly. However, the response was dependent on the endogenous expression of 17HSD type 1. Expression of 17HSD type 1 seems to be dominant to 17HSD type 2. Therefore, it may be important to investigate a ratio between 17HSD type 1 and 17HSD type 2.

scholarly journals Reducing Selenoprotein F Promotes the Transformation of Immortalized Prostate Epithelial Cells

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1809-1809
Author(s):  
Lenny Hong ◽  
Mostafa Elhodaky ◽  
Shrinidhi Kadkol ◽  
Alan Diamond
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Cancer Progression ◽  
Tca Cycle ◽  
Soft Agar ◽  
Metabolic Shift ◽  
Normal Prostate ◽  
Funding Sources ◽  
Prostate Cells ◽  
Prostate Epithelial Cells

Abstract Objectives Selenoprotein F (SELENOF) levels are responsive to available dietary selenium and found in high levels in benign prostate cells. It is implicated in prostate cancer (PCa) mortality due to associations between polymorphisms in the corresponding gene and death from the disease. SELENOF levels are dramatically lower in prostate cancer compared to adjacent benign tissue. The objective of this study was to determine whether reducing SELENOF levels in human, non-transformed RWPE-1 prostate epithelial cells alters their phenotype to implicate SELENOF loss in PCa progression. Methods SELENOF levels were reduced in RWPE-1 cells that express high levels of SELENOF using a SELENOF shRNA construct. Proliferation was determined by quantifying DNA using fluorometric dsDNA quantitation. Growth in soft agar and cell mobility of cells in culture (wound healing assay) were imaged using an Evos FL microscope and quantified using Image J software. The oxygen consumption rate (OCR) was measured using a Seahorse XFe24 Analyzer. Results SELENOF levels were reduced in RWPE-1 and these cells exhibited decreased contact inhibition in culture (n = 3, P < 0.001) when compared to controls. Normal prostate epithelial cells are atypical in that they rely on glycolysis for energy production, have a truncated TCA cycle, and a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) occurs in PCa. Reducing SELENOF in RWPE-1 cells resulted in higher OCR compared to controls, indicating that SELENOF can impact the sources and pathways used in cellular energy metabolism. Conclusions Reduced SELENOF levels in RWPE-1 prostate cells resulted in properties consistent with a transformed phenotype and an increase in OCR, and indicating that the reduction in SELENOF may contribute a metabolic shift towards a PCa cancer-like metabolism. Together, these results indicate that SELENOF loss likely contributes to cancer progression. Funding Sources This work was supported by a grant from the Department of Defense to AMD and a Pre-Doctoral Education for Clinical and Translational Scientists Fellowship to LKH.

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