The role of heat shock protein 70 in the thermoresistance of prostate cancer cell line spheroids

We investigated the presence of glucocorticoid receptors (GR) as well as the role of glucocorticoids (Gc) in the control of proliferation of the androgen-independent prostate cancer cell line, DU145. We detected the presence of a specific high affinity binding site (K(d) 2.3 nM) for [(3)H]dexamethasone ([(3)H]Dex) in the cytosolic preparations of DU145 cells; the density of these binding sites is significantly higher than that detected in HA22T/VGH and in HepG2, two hepatoma cell lines classically considered models for the study of GR. Immunocytochemistry studies confirmed the presence of GR in the cytosolic compartment of DU145 cells; GR undergo translocation to the nucleus following exposure to dexamethasone (Dex). The functional activity of GR present in DU145 cells was also studied by analyzing the potency of Dex in inducing chloramphenicol acyltransferase (CAT) activity in DU145 cells transfected with a glucocorticoid/progesterone response element (GRE/PRE) tkCAT plasmid (GRE/PREtkCAT plasmid). The results have shown that Dex stimulates the transcriptional activity of GR in transfected DU145 cells with an EC(50) of 9.65 nM and a maximal induction of sevenfold above basal levels. Finally, a dose-dependent (IC(50) 3.14 nM) decrease of DU145 cell numbers was observed after their exposure to Dex for 4 days; this effect was counteracted by the presence of the steroid antagonist, RU486. In conclusion, the present data suggest a possible role of corticoids in the control of the growth of androgen-independent prostate cancer.

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Heat–Induced Cellular Damage and Tolerance in Combination with Adriamycin for the PC–3 Prostate Cancer Cell Line: Relationships with Cytotoxicity, Reactive Oxygen Species and Heat Shock Protein 70 Expression

European Urology ◽

10.1159/000020285 ◽

2000 ◽

Vol 38 (2) ◽

pp. 235-240 ◽

Cited By ~ 8

Author(s):

N. Moriyama-Gonda ◽

M. Igawa ◽

H. Shiina ◽

S. Urakami ◽

Y. Wada ◽

...

Keyword(s):

Prostate Cancer ◽

Reactive Oxygen Species ◽

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Protein 70 ◽

Prostate Cancer Cell ◽

Cancer Cell Line ◽

Prostate Cancer Cell Line ◽

Cellular Damage ◽

Oxygen Species

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Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion

Nature Communications ◽

10.1038/s41467-020-18313-y ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Bianca Cioni ◽

Anniek Zaalberg ◽

Judy R. van Beijnum ◽

Monique H. M. Melis ◽

Johan van Burgsteden ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cell Line ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Line ◽

Prostate Cancer Cell Line ◽

Migration And Invasion ◽

Receptor Signalling

Abstract The androgen receptor (AR) is the master regulator of prostate cancer (PCa) development, and inhibition of AR signalling is the most effective PCa treatment. AR is expressed in PCa cells and also in the PCa-associated stroma, including infiltrating macrophages. Macrophages have a decisive function in PCa initiation and progression, but the role of AR in macrophages remains largely unexplored. Here, we show that AR signalling in the macrophage-like THP-1 cell line supports PCa cell line migration and invasion in culture via increased Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) signalling and expression of its downstream cytokines. Moreover, AR signalling in THP-1 and monocyte-derived macrophages upregulates IL-10 and markers of tissue residency. In conclusion, our data suggest that AR signalling in macrophages may support PCa invasiveness, and blocking this process may constitute one mechanism of anti-androgen therapy.

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