Neuronal differentiation of PC12 cells abolishes the expression of membrane androgen receptors

Alexaki, Vasileia Ismini; Dermitzaki, Eirini; Charalampopoulos, Ioannis; Kampa, Marilena; Nifli, Artemissia-Phoebe; Gravanis, Achille; Margioris, Andrew N.; Castanas, Elias

doi:10.1016/j.yexcr.2006.04.023

Cited by 12 publications

(6 citation statements)

References 73 publications

(143 reference statements)

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“…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). Here, we show for the first time that mER, mAR, and mAR are almost constantly coexpressed in tumor cells (but not in the surrounding nontumoral tissue), indicating a possible common regulation of all three proteins during the malignant transformation of breast tissue.…”

Section: Epo-epor and Steroid Receptors In Breast Cancermentioning

confidence: 61%

“…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%

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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: Epo-epor and Steroid Receptors In Breast Cancermentioning

confidence: 61%

Section: Immunohistochemical Staining Of Epo and Epormentioning

confidence: 99%

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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“…Most recently, membrane androgen receptors transmitting rapid androgen signals have been characterized biochemically in several cell types including macrophages and T cells (8,19), LNCaP (9), T47D (15), MCF7 (20), DU145 (21), C6 (22), PC12 (23), or VSMC cells (24). Signals emanating from this receptor result in increased intracellular [Ca 21 ] and inositol 1,4,5-triphosphate formation, cannot be blocked by anti-androgens (9,25) and are sensitive to pertussis toxin inhibition indicating that mAR may actually be a GPCR (14)(15)(16).…”

Section: Introductionmentioning

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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“…This is an important distinction in technique and expense as charcoal stripped-FBS is twice the cost of FBS. While AR is expressed in LNCaP cells, ARs are down-regulated in NGF differentiated PC-12 cells [36]. Mechanistically, it's likely that the distinction generalizes to pursing two distinct strategies depending on the presence or absence of known ligand-dependent, PAK-6 interacting proteins such as AR or ERα.…”

Section: Introductionmentioning

confidence: 99%

Detection of the steroid receptor interacting protein, PAK6, in a neuronal cell line

Goyette¹,

Schott

Uwimana

et al. 2019

Heliyon

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PAK6 is a Group II p21 activated kinase that unlike traditional signal transduction proteins interacts with multiple binding partners including sex-steroid receptors. PAK6 acts as a nodal checkpoint integrating multiple cellular inputs to promote distinct cellular outcomes, some of which are associated with cytoskeletal remodeling. Despite the possibility that PAK6 may couple sex-specific neuronal function and therefore serve as a valuable research, diagnostic and therapeutic target, there is currently no standardized protocol for assessing PAK6 activity in a neuronal cell line. Here, we present a protocol for assessing PAK6 levels in a commonly used neuronal cell line, PC-12. In comparison with other methodology, this approach (1) does not require ex-planted tissue to identify PAK6 in neurons and (2) unlike other protocols which require steroid depleted media for detection of PAK6 in non-neuronal cell lines, such as prostate cancer cell lines, we were easily able to detect PAK6 in PC-12 cells grown in complete, steroid-containing media. Thus the present protocol allows for the efficient detection of native PAK6 in PC-12 cells to expedite targeted basic research of the emerging importance of PAK6 function in the brain as well as to accelerate the identification and isolation of potential therapeutic targets not only in cancerous but brain disease states as well.

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Neuronal differentiation of PC12 cells abolishes the expression of membrane androgen receptors

Cited by 12 publications

References 73 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

Detection of the steroid receptor interacting protein, PAK6, in a neuronal cell line

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