Both retinoids and androgens are required to maintain or promote functional differentiation in reaggregation cultures of human prostate epithelial cells

Goossens, Karine; Deboel, Ludo; Swinnen, Johannes V.; Roskams, Tania; Manin, M.; Rombauts, Wilfried; Verhoeven, Guido

doi:10.1002/pros.10125

Cited by 16 publications

(12 citation statements)

References 52 publications

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“…4A), suggesting that removing EGF was not sufficient to promote differentiation. We then supplemented EGF‐deficient culture medium with a cocktail of factors that have shown differentiating activity in prostate and other types of cells (Peehl et al, 1993; Danielpour, 1999; Zhao et al, 1999; Goossens et al, 2002). The individual factors in the cocktail, designated as “VRT,” were 1,25‐dihydroxyvitamin D 3 (10 nM), all‐trans retinoic acid (1 μM) and TGF‐β1 (1 ng/ml).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of monoamine oxidase A promotes secretory differentiation in basal prostatic epithelial cells

et al. 2008

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Monoamine oxidase A (MAO-A) expression is associated with high-grade prostate cancer. Immunohistochemistry showed that MAO-A is also expressed in the basal epithelial cells of normal prostate glands. Using cultured primary prostatic epithelial cells as a model, we showed that MAO-A prevents basal epithelial cells from differentiating into secretory cells. Under differentiationpromoting conditions, clorgyline, an irreversible MAO-A inhibitor, induced secretory cell-like morphology and repressed expression of cytokeratin 14, a basal cell marker. More importantly, clorgyline induced mRNA and protein expression of androgen receptor (AR), a hallmark of secretory epithelial cells. In clorgyline-treated cells, androgen induced luciferase activity controlled by the promoter of prostate-specific antigen, an AR target gene, in a dose-dependent manner. This activity was blocked by the AR antagonist Casodex, showing that AR is functional. In turn, androgen decreased MAO-A expression in clorgyline-treated, secretory-like cells. Our results demonstrated that cultured basal epithelial cells have the potential to differentiate into secretory cells, and that inhibition of MAO-A is a key factor in promoting this process. Increased expression of MAO-A in high-grade prostate cancer may be an important contributor to its de-differentiated phenotype, raising the possibility that MAO-A inhibition may restore differentiation and reverse the aggressive behavior of high-grade cancer.

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Section: Resultsmentioning

confidence: 99%

Inhibition of monoamine oxidase A promotes secretory differentiation in basal prostatic epithelial cells

et al. 2008

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“…Three‐dimensional aggregates are considered to be superior to monolayer cell cultures in terms of communication between cells and maintenance of tissue‐specific gene expression in a variety of organs (61–67). In the present study, we compared cell type distribution in the aggregates with that of the 14‐day‐old rat pituitary gland.…”

Section: Discussionmentioning

confidence: 99%

Triiodothyronine Expands the Lactotroph and Maintains the Lactosomatotroph Population, Whereas Thyrotrophin‐Releasing Hormone Augments Thyrotroph Abundance in Aggregate Cell Cultures of Postnatal Rat Pituitary Gland

Pals

Vankelecom

Denef

2006

J Neuroendocrinology

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In the present study, we used a three-dimensional pituitary cell culture system from early postnatal rats to examine the in vitro developmental potential of triiodothyronine (T3) and thyrotrophin-releasing hormone (TRH). Cell types were identified at the hormone mRNA level by single-cell reverse transcription-polymerase chain reaction and any change in abundance was further examined by immunofluorescence staining of the corresponding hormone protein. In aggregates from 14-day-old rats, long-term (12-16 days) treatment with T3 (0.5 nM) increased the abundance of cells expressing prolactin mRNA (PRLmRNA cells) by 2.5-fold and lowered that of nonhormonal cells and thyroid-stimulating hormone beta (TSHbeta)mRNA cells. The abundance of growth hormone (GH)mRNA cells decreased during culture compared to that in the freshly dispersed pituitary gland and T3 did not significantly affect this cell population. Cells coexpressing PRL mRNA and GH mRNA virtually disappeared during culture but reappeared in the presence of T3. T3 increased the abundance of PRL-immunoreactive (ir) cells in aggregates from 14-day-old rats, as well as in aggregates from newborn and 1-week-old rats. As estimated by bromodeoxyuridine (BrdU) labelling, a 3-day treatment with T3 enhanced the number of PRL-ir cells that had incorporated BrdU, but did not yet expand the total population of PRL-ir cells. Long-term treatment with TRH (100 nM) did not affect the proportion of PRLmRNA or GHmRNA cells, but consistently increased the proportional number of TSHbeta(mRNA) and TSHbeta-ir cells. The present data confirm the findings obtained in recent in vivo loss of function genetic studies suggesting that T3 plays a prominent role in postnatal expansion of the lactotroph population and that TRH is important for thyrotroph development. The data suggest that the effect of T3 is brought about by a direct action on the pituitary gland through a cell proliferation mechanism. T3 also appears to support the lactosomatotroph population. In view of the established theory that lactotrophs develop from GH-expressing progenitor cells and that this is a post mitotic event, we propose that T3 is mitogenic for GHmRNA cells that lack GH-ir material and that transdifferentiate into PRL-ir cells, but that a pathway of PRL cell development from mitotic nonhormonal cell progenitors may also be involved.

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“…These cells are typified by proliferation and simultaneous expression of markers of both basal and secretory cells, and are believed to be progenitor cells in the process of differentiating [Bonkhoff et al, 1994]. Analyses of additional markers of basal and secretory cells have shown that, indeed, primary cultures are populated by cells that have characteristics of both types of cells [van Leenders et al, 2000;Liu and Peehl, 2001;Goossens et al, 2002;Tran et al, 2002;Garraway et al, 2003].…”

Section: Cytokeratinsmentioning

confidence: 94%

Are primary cultures realistic models of prostate cancer?

Peehl

2003

J of Cellular Biochemistry

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Primary cultures fill a unique niche among the repertoire of in vitro model systems available to investigate the biology of the normal and malignant human prostate. This review summarizes some of the properties of primary cultures, with special emphasis on two questions: are primary cultures from adenocarcinomas really comprised of cancer rather than normal cells, and do primary cultures faithfully retain characteristics of cells of origin?

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Both retinoids and androgens are required to maintain or promote functional differentiation in reaggregation cultures of human prostate epithelial cells

Abstract: A combination of retinoids and androgens is able to preserve, for a prolonged period of time, some degree of secretory differentiation in freshly isolated PEC maintained in reaggregation culture. The same combination is unable to restore secretory differentiation in subcultured PEC.

Cited by 16 publications

References 52 publications

Inhibition of monoamine oxidase A promotes secretory differentiation in basal prostatic epithelial cells

Inhibition of monoamine oxidase A promotes secretory differentiation in basal prostatic epithelial cells

Triiodothyronine Expands the Lactotroph and Maintains the Lactosomatotroph Population, Whereas Thyrotrophin‐Releasing Hormone Augments Thyrotroph Abundance in Aggregate Cell Cultures of Postnatal Rat Pituitary Gland

Are primary cultures realistic models of prostate cancer?

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