Membrane Androgen Receptor Activation Induces Apoptotic Regression of Human Prostate Cancer Cells<i>in Vitro</i>and<i>in Vivo</i>

Hatzoglou, Anastassia; Kampa, Marilena; Kaiser, Christina; Charalampopoulos, Ioannis; Theodoropoulos, Panayiotis A.; Anezinis, Ploutarchos; Dambaki, Constantina; Papakonstanti, Evangelia A.; Stathopoulos, Efstathios N.; Stournaras, Christos; Gravanis, Achille; Castanas, Elias

doi:10.1210/jc.2004-0801

Cited by 128 publications

(144 citation statements)

References 36 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…12 Earlier binding studies in prostate and colon cancer cells established the optimal concentration of testosterone-HSA treatments. 2,12,16 Accordingly, testosterone-HSA solution was used at a final concentration of 10 27 mol l 21 throughout the study. 12 If not otherwise mentioned, all treatments and incubations with steroids including apoptosis assays were performed in serum-containing medium.…”

Section: Preparation Of Steroid Solutionmentioning

confidence: 99%

“…[2][3][4][5][6][7] Activation of these binding sites by no permeable testosterone albumin conjugates (TACs), was shown to induce strong proapoptotic and anti-tumorigenic effects on various tumors both in vitro and in vivo. 2,6,8,9 The molecular mechanisms governing these effects have been elucidated and specific signaling cascades triggered by the stimulation of membrane androgen receptors (mARs) have been described in prostate and breast tumor cells. 4,5,[9][10][11] Functional membrane androgen binding sites have been also reported in colon cancer cells and tissues.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Testosterone induced apoptosis in colon cancer cells is regulated by PI3K/Rac1 signaling

Alkahtani¹

2013

Asian J Androl

View full text Add to dashboard Cite

Recently, it has been reported that testosterone membrane signaling regulates actin reorganization and induces pro-apoptotic responses in colon tumor cells. In the present study the membrane androgen receptors (mARs)-induced activation of Rac1 GTPase and the involvement of PI3K/Rac1 signaling in controlling the apoptotic responses in testosterone treated Caco2 colon cancer cells has been analyzed. In line with previous findings, activation of mAR by testosterone conjugates triggered early and transient actin reorganization as indicated by the significant decrease of the G/Total actin ratio after 15-and 30-min treatment of the cells. Interestingly, stimulation of mAR rapidly activated the Rac1 GTPase. This effect was evident after 15 min and persisted for at least 24 h. Testosterone induced Rac1 activation was fully blocked in Caco2 cells pre-treated with the PI3K inhibitor wortmannin, indicating that Rac1 signaling is acting downstream of the PI3K pathway. Remarkably, when cells were pre-treated with wortmannin that blocks the PI3K/Rac1 signaling, apoptotic response was almost fully inhibited. These finding suggest that Rac1 activation, triggering actin redistribution, is involved in testosterone induced pro-apoptotic responses governed by mAR activation and emphasize the regulatory role of PI3K/Rac1 signaling in colon tumors.

show abstract

Section: Preparation Of Steroid Solutionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Testosterone induced apoptosis in colon cancer cells is regulated by PI3K/Rac1 signaling

Alkahtani¹

2013

Asian J Androl

View full text Add to dashboard Cite

show abstract

“…The existence of a novel membrane-bound AR has been postulated by a number of authors based on the detection of specific androgen binding to plasma membranes in different cell types including endothelial cells [84], breast cancer cells [85], prostate cancer cells [83], osteoblasts [86], macrophages [58], and T-lymphocytes [26; 28; 87]. The ability of androgens to rapidly modulate the activity of ion channels and [Ca 2+ ] i has been observed in several cell types.…”

Section: Membrane Receptorsmentioning

confidence: 99%

Non-genomic actions of androgens

Foradori

Weiser

Handa

2008

Frontiers in Neuroendocrinology

406

244

View full text Add to dashboard Cite

Previous work in the endocrine and neuroendocrine fields has viewed androgen receptors (AR) as a transcription factor activated by testosterone or one of its many metabolites. The bound androgen receptor acts as transcription factor and binds to specific DNA response elements in target gene promoters, causing activation or repression of transcription and subsequently protein synthesis. Over the past two decades evidence has begun to accumulate to implicate androgens, dependent or independent of the AR, in rapid actions at the cellular and organism level. Androgen's rapid time course of action; effects in the absence or inhibition of the cellular machinery necessary for transcription/translation; and/or the effects of androgens not able to translocate to the nucleus suggest a method of androgen action not initially dependent on genomic mechcanisms (i.e. non-genomic in nature). In the present paper the non-genomic effects of androgens are reviewed, along with a discussion of the possible role non-genomic androgen actions have on animal physiology and behavior.

show abstract

“…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%

“…Steroids, acting via membrane sites, exert short-term pharmacologic actions different from those of intracellular receptors, including ion mobilization, hormone or enzyme secretion, and cytoskeleton modifications (25)(26)(27)(28)(29), possibly involved in several physiologic or pathologic processes, including cancer. Indeed, androgen membrane receptors (mAR) are expressed in human prostate carcinomas (30) and correlate to the differentiation grade of the tumor, expressed by the Gleason score (31), although their activation inhibits the growth of experimental tumors in animals (32,33). In breast cancer cells, estrogen membrane receptor (mER) and mAR exert opposing effects, promoting survival (mER) or apoptosis (mAR; ref.…”

Section: Introductionmentioning

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

Self Cite

View full text Add to dashboard Cite

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)

show abstract

Membrane Androgen Receptor Activation Induces Apoptotic Regression of Human Prostate Cancer Cellsin Vitroandin Vivo

Cited by 128 publications

References 36 publications

Testosterone induced apoptosis in colon cancer cells is regulated by PI3K/Rac1 signaling

Testosterone induced apoptosis in colon cancer cells is regulated by PI3K/Rac1 signaling

Non-genomic actions of androgens

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

Contact Info

Product

Resources

About