Membrane testosterone binding sites in prostate carcinoma as a potential new marker and therapeutic target: Study in paraffin tissue sections

Dambaki, Constantina; Kaiser, Christina; Kampa, Marilena; Darivianaki, Katherine; Nomikos, Michael; Anezinis, Ploutarchos; Theodoropoulos, Panayiotis A.; Castanas, Elias; Stathopoulos, Efstathios N.

doi:10.1186/1471-2407-5-148

Cited by 31 publications

(28 citation statements)

References 22 publications

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“…2A to D, respectively. Nontumoral breast tissue was negative for membrane steroid receptors, as was previously reported in prostate cancer (30,31). mER was slightly more abundant than mPR and mAR in cases in which preoperative chemotherapy had been administered (7.3 F 1.7 and 9.3 F 0.5 positive counts for mER, 10.0 F 2.0 and 8.0 F 0.5 for mPR, and 10.6 F 1.6 and 8.8 F 0.5 for mAR, in patients who had not or had received preoperative chemotherapy, respectively).…”

Section: Resultssupporting

confidence: 60%

“…For the detection of membrane steroid receptors, a (partial) regeneration of membrane proteins was done as described previously (31). Briefly, after a mild melting of the embedding medium at 42.5jC for 20 min, slides were dewaxed and rehydrated, incubated (37jC, 2 h) in citrate buffer (0.01 mol/L, pH 6.2), and washed in TBS (10 mmol/L, NaCl 150 mmol/L, pH 7.4).…”

Section: Immunohistochemical Staining Of Epo and Epormentioning

confidence: 99%

“…Our previous data, both in breast cancer cells (34) as well as on cells of different origin (PC12 pheochromocytoma cells; ref. 36), brain tissue (37), and prostate cancer (26,28,31,32), indicate that (a) steroid-specific antagonists do not modify the membrane binding characteristics of steroids, suggesting a different primary structure of the molecules (28,30,31); (b) saturation with high concentrations of steroids decreases the binding (37); and (c) BSA saturation decreases nonspecific binding of the protein-steroid conjugate on membranes (30). Based on these considerations, we advanced the above method for the tracing of membrane steroid receptors.…”

Section: Immunohistochemical Staining Of Epo and Epormentioning

confidence: 99%

“…24 for a recent review). We have previously shown that mAR is expressed in prostate cancer (31), being correlated with the Gleason score, although their activation induces regression of human prostate tumor xenografts (33) and potentiates the effect of cytoskeletal acting agents (34), suggesting a new potential cancer therapeutic target. Finally, in breast cancer cell lines and PC12 pheochromocytoma cells, mER and mAR exert opposing effects on growth, apoptosis, and secretion (34,36).…”

Section: Epo-epor and Steroid Receptors In Breast Cancermentioning

confidence: 99%

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Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome

Pelekanou

Kampa

Kafousi³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Autocrine/paracrine erythropoietin (EPO) action, promoting cell survival and mediated by its receptor (EPOR) in various solid tumors, including breast carcinoma, questions about the prognostic and therapeutic interest of this system. The expression of EPO/EPOR is steroid dependent in some tissues; however, a clear relationship of EPO/EPOR and steroid receptors in breast cancer has not been established thus far. Recently, the field of steroid receptors has expanded, including rapid effects mediated by membrane-associated receptors, regulating cell survival or apoptosis. The aim of this study was to evaluate EPO/EPOR and membrane-associated steroid receptor expression in breast carcinoma, in view of their prognostic significance, compared with other established markers [estrogen receptor (ER)-progesterone receptor (PR) status and Her2 expression] and hypoxia-induced factor 1 nuclear localization in 61 breast cancer specimens followed for V90 months. We report that EPO-EPOR were expressed in 80% and 84% of samples, although 8% and 2% of nontumoral fields expressed EPO/EPOR too. Membrane-associated receptors for estrogen (mER), progesterone (mPR), and androgen (mAR) were expressed in 96%, 94%, and 93% of cases. Significant correlations between EPO-hypoxiainduced factor 1A, mER-ER, mER-EPO, mAR-EPOR, and mER-mPR-Her2 were found. Finally, EPO, EPOR, and mAR are inversely related to disease-free and overall survival. However, in view of the above correlations, we conclude that EPO/EPOR and membrane steroid receptors are not independent prognostic markers as they are closely related to other established markers. In contrast, they may represent possible new therapeutic targets. (Cancer Epidemiol Biomarkers Prev 2007; 16(10):2016-23)

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Section: Resultssupporting

confidence: 60%

Section: Immunohistochemical Staining Of Epo and Epormentioning

confidence: 99%

Section: Immunohistochemical Staining Of Epo and Epormentioning

confidence: 99%

Section: Epo-epor and Steroid Receptors In Breast Cancermentioning

confidence: 99%

See 2 more Smart Citations

Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome

Pelekanou

Kampa

Kafousi³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

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“…To that extent, membrane androgen receptor combines several characteristics that justify development of specific mAR ligands as novel drug candidates for prostate cancer treatment. First, mAR is selectively over-expressed in biopsy samples from aggressive, high-Gleason prostate tumors in comparison to samples from benign prostate hyperplasia patients or healthy subjects (45,46). Second, prototype mAR ligands comprising albumin conjugated androgens (testosterone-BSA conjugates) induce apoptotic regression of prostate cancer cells in vitro and in vivo (21,26).…”

Section: Membrane Androgen Receptor: a Target For Therapeutic Intervementioning

confidence: 99%

Membrane androgen receptor activation in prostate and breast tumor cells: Molecular signaling and clinical impact

et al. 2008

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In recent years, membrane androgen receptors (mARs) have been identified in prostate and breast tumor cells, and their activation by specific mAR ligands was linked to the regulation of crucial cell responses, such as cell growth, motility, and apoptosis. Analysis of the molecular signals triggered by mAR in the presence of anti‐androgens has clearly differentiated mAR‐dependent biological actions from those induced by the activation of the classical intracellular androgen receptors (iARs). In this review, we summarize the specific cellular events attributed to mAR activation and the experimental results on distinct non‐genomic signaling cascades operating in various tumor cells independently of the iAR. Furthermore, we discuss the crucial role of actin cytoskeleton organization and signaling in mediating mAR responses. Finally, we assess the clinical impact of the reported mAR‐induced apoptotic regression of prostate cancer cells both in vitro and in vivo and discuss the potential role of mAR as a novel therapeutic target. © 2008 IUBMB IUBMB Life, 61(1): 56–61, 2009

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The role of androgen in determining differentiation and regulation of androgen receptor expression in the human prostatic epithelium transient amplifying population

Heer

Robson

Shenton

et al. 2007

Journal Cellular Physiology

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Abnormal differentiation in epithelial stem cells or their immediate proliferative progeny, the transiently amplifying population (TAP), may explain malignant pathogenesis in the human prostate. These models are of particular importance as differing sensitivities to androgen among epithelial cell subpopulations during differentiation are recognised and may account for progression to androgen independent prostate cancer. Androgens are crucial in driving terminal differentiation and their indirect effects via growth factors from adjacent androgen responsive stroma are becoming better characterised. However, direct effects of androgen on immature cells in the context of a prostate stem cell model have not been investigated in detail and are studied in this work. In alpha2beta1hi stem cell enriched basal cells, androgen analogue R1881 directly promoted differentiation by the induction of differentiation-specific markers CK18, androgen receptor (AR), PSA and PAP. Furthermore, treatment with androgen down-regulated alpha2beta1 integrin expression, which is implicated in the maintenance of the immature basal cell phenotype. The alpha2beta1hi cells were previously demonstrated to lack AR expression and the direct effects of androgen were confirmed by inhibition using the anti-androgen bicalutamide. AR protein expression in alpha2beta1hi cells became detectable when its degradation was repressed by the proteosomal inhibitor MG132. Stratifying the alpha2beta1hi cells into stem (CD133(+)) and transient amplifying population (TAP) (CD133(-)) subpopulations, AR mRNA expression was found to be restricted to the CD133(-) (TAP) cells. The presence of a functional AR in the TAP, an androgen independent subpopulation for survival, may have particular clinical significance in hormone resistant prostate cancer, where both the selection of immature cells and functioning AR regulated pathways are involved.

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Membrane testosterone binding sites in prostate carcinoma as a potential new marker and therapeutic target: Study in paraffin tissue sections

Cited by 31 publications

References 22 publications

Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome

Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome

Membrane androgen receptor activation in prostate and breast tumor cells: Molecular signaling and clinical impact

The role of androgen in determining differentiation and regulation of androgen receptor expression in the human prostatic epithelium transient amplifying population

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