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Membrane androgen receptor activation triggers pro-apoptotic responses in vitro and in vivo and blocks migration in colon cancer

von S. G.

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[1.] Shg/Fragment 017 01 - Diskussion
Zuletzt bearbeitet: 2014-11-02 01:26:47 Hindemith
Fragment, Gesichtet, Gu et al 2009, KomplettPlagiat, SMWFragment, Schutzlevel sysop, Shg

Typus
KomplettPlagiat
Bearbeiter
Graf Isolan
Gesichtet
Yes.png
Untersuchte Arbeit:
Seite: 17, Zeilen: 1-14
Quelle: Gu et al 2009
Seite(n): 1-2, Zeilen: 1: li.Sp.1-2 - re.Sp. 1-3 - 2: li.Sp. 1-9
1.1.2. Membrane Androgen Receptor

Scientific evidence accumulated in recent year’s [sic] points to the existence of membrane androgen receptors (mARs), triggering rapid, non-genomic signals. Although the exact molecular identity of mAR still remains unknown, non-genomic androgen actions manifested within minutes have been reported in various cell types including macrophages and T cells [Benten WP, et al. 1999; Benten WP, et al. 1999], LNCaP [Kampa M, et al. 2002; Wang Z, et al. 2008], T47D [Kampa M, et al. 2005], MCF7 [Kallergi G, et al. 2007], DU145 [Hatzoglou A, et al. 2005; Papadopoulou N, et al. 2008a; Papadopoulou N, et al 2008b], C6 [Gatson JW, et al. 2006], PC12 [Alexaki VI, et al. 2006] or VSMC cells [Somjen D, et al 2004]. These effects are clearly different from those manifested upon activation of the intracellular androgen receptors (iARs) mediating genomic androgen signals resulting in receptor dimerization, nuclear translocation and subsequent activation of androgen-specific target genes.


Alexaki VI, Charalampopoulos I, Kampa M, Nifli AP, Hatzoglou A, Gravanis A, Castanas E. (2006). Activation of membrane estrogen receptors induce pro-survival kinases. J Steroid Biochem Mol Biol. 98:97-110.

Benten WP, et al. (1999a). Testosterone signaling through internalizable surface receptors in androgen receptor-free macrophages. Mol Biol Cell10: 3113-3123.

Benten WP, et al.(1999b). Functional testosterone receptors in plasma membranes of T cells. Faseb J, 13:123-133.

Gatson JW, Kaur P, Singh M. (2006). Dihydrotestosterone differentially modulates the mitogen-activated protein kinase and the phosphoinositide 3-kinase/Akt pathways through the nuclear and novel membrane androgen receptor in C6 cells. Endocrinology 147:2028-2034.

Hatzoglou A, Kampa M, Kogia C, Charalampopoulos I, Theodoropoulos PA, Anezinis P, Dambaki C, Papakonstanti EA, Stathopoulos EN, Stournaras C, et al. (2005). Membrane androgen receptor activation induces apoptotic regression of human prostate cancer cells in vitro and in vivo. J Clin Endocrinol Metab, 90: 893-903.

Kallergi G, Agelaki S, Markomanolaki H, Georgoulias V, Stournaras C. (2007). Activation of FAK/PI3K/Rac1 signaling controls actin reorganization and inhibits cell motility in human cancer cells. Cell Physiol Biochem, 20:977-986.

Kampa M, Papakonstanti EA, Hatzoglou A, Stathopoulos EN, Stournaras C, Castanas E. (2002). The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors that increase PSA secretion and modify actin cytoskeleton. Faseb J, 16:1429-1431.

Kampa M, Kogia C, Theodoropoulos PA, Anezinis P, Charalampopoulos I, Papakonstanti EA, Stathopoulos EN, Hatzoglou A, Stournaras C, Gravanis A, Castanas E. (2006) Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells. Mol Cancer Ther, 5:1342-1351.

Papadopoulou N, Charalampopoulos I, Alevizopoulos K, Gravanis A, Stournaras C. (2008 a). Rho/ROCK/Actin signaling regualtes membrane androgen receptor induced apoptosis in prostate cancer cells. Exp Cell Res, 314: 3162-3174.

Papadopoulou N, Charalampopoulos I, Anagnostopoulou V, Konstantinidis G, Föller M, Gravanis A, Alevizopoulos K, Lang F, Stournaras C. (2008 b). Membrane androgen receptor activation triggers down-regulation of PI-3K/Akt/NF-kappaB activity and induces apoptotic responses via Bad, FasL and caspase-3 in DU-145 prostate cancer cells. Mol Canc. 7:88.

Somjen D, Kohen F, Gayer B, Kulik T, Knoll E, Stern N. (2004). Role of putative membrane receptors in the effect of androgens on human vascular cell growth. J Endocrinol. 180:97-106.

Wang Z, Liu L, Hou J, Wen D, Yan C, Pu J, Ouyang J, Pan H. (2008). Rapid membrane effect of testosterone in LNCaP cells. Urol Int.81(3):353-9

[Seite 1]

Introduction

Scientific evidence accumulated in recent years points to the existence of membrane androgen receptors (mAR), triggering rapid, non-genomic signals. Although the exact molecular identity of mAR still remains unknown, nongenomic androgen actions manifested within minutes

[Seite 2]

have been reported in various cell types including macrophages and T cells [1,2], LNCaP [3,4], T47D [5], MCF7 [6], DU145 [7-9], C6 [10], PC12 [11] or VSMC cells [12]. These effects are clearly different from those manifested upon activation of the intracellular androgen receptors (iAR) mediating genomic androgen signals resulting in receptor dimerization, nuclear translocation and subsequent activation of androgen-specific target genes (reviewed in [13]).


1. Benten WP, Lieberherr M, Stamm O, Wrehlke C, Guo Z, Wunderlich F: Testosterone signaling through internalizable surface receptors in androgen receptor-free macrophages. Mol Biol Cell 1999, 10:3113-3123.

2. Benten WP, Lieberherr M, Giese G, Wrehlke C, Stamm O, Sekeris CE, Mossmann H, Wunderlich F: Functional testosterone receptors in plasma membranes of T cells. Faseb J 1999, 13:123-133.

3. Kampa M, Papakonstanti EA, Hatzoglou A, Stathopoulos EN, Stournaras C, Castanas E: The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors that increase PSA secretion and modify actin cytoskeleton. Faseb J 2002, 16:1429-1431.

4. Wang Z, Liu L, Hou J, Wen D, Yan C, Pu J, Ouyang J, Pan H: Rapid membrane effect of testosterone in LNCaP cells. Urol Int 2008, 81(3):353-359.

5. Kampa M, Kogia C, Theodoropoulos PA, Anezinis P, Charalampopoulos I, Papakonstanti EA, Stathopoulos EN, Hatzoglou A, Stournaras C, Gravanis A, Castanas E: Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells. Mol Cancer Ther 2006, 5:1342-1351.

6. Kallergi G, Agelaki S, Markomanolaki H, Georgoulias V, Stournaras C: Activation of FAK/PI3K/Rac1 signaling controls actin reorganization and inhibits cell motility in human cancer cells. Cell Physiol Biochem 2007, 20:977-986.

7. Hatzoglou A, Kampa M, Kogia C, Charalampopoulos I, Theodoropoulos PA, Anezinis P, Dambaki C, Papakonstanti EA, Stathopoulos EN, Stournaras C, Gravanis A, Castanas E: Membrane androgen receptor activation induces apoptotic regression of human prostate cancer cells in vitro and in vivo. J Clin Endocrinol Metab 2005, 90:893-903.

8. Papadopoulou N, Charalampopoulos I, Alevizopoulos K, Gravanis A, Stournaras C: Rho/ROCK/Actin signaling regualtes membrane androgen receptor induced apoptosis in prostate cancer cells. Exp Cell Res 2008, 314:3162-3174.

9. Papadopoulou N, Charalampopoulos I, Anagnostopoulou V, Konstantinidis G, Föller M, Gravanis A, Alevizopoulos K, Lang F, Stournaras C: Membrane androgen receptor activation triggers down-regulation of PI-3K/Akt/NF-kappaB activity and induces apoptotic responses via Bad, FasL and caspase-3 in DU-145 prostate cancer cells. Mol Canc 2008, 7:88.

10. Gatson JW, Kaur P, Singh M: Dihydrotestosterone differentially modulates the mitogen-activated protein kinase and the phosphoinositide 3-kinase/Akt pathways through the nuclear and novel membrane androgen receptor in C6 cells. Endocrinology 2006, 147:2028-2034.

11. Alexaki VI, Charalampopoulos I, Kampa M, Nifli AP, Hatzoglou A, Gravanis A, Castanas E: Activation of membrane estrogen receptors induce pro-survival kinases. J Steroid Biochem Mol Biol 2006, 98:97-110.

12. Somjen D, Kohen F, Gayer B, Kulik T, Knoll E, Stern N: Role of putative membrane receptors in the effect of androgens on human vascular cell growth. J Endocrinol 2004, 180:97-106.

13. Heinlein CA, Chang C: Androgen receptor in prostate cancer. Endocr Rev 2004, 25:276-308.

Anmerkungen

Obwohl Shg als Coautor von Gu et al (2009) genannt wird, stammt keine der Formulierungen dieses Artikels von Shg (vgl. die Anmerkungen zu Quelle:Shg/Gu_et_al_2009).

Ergo: Übernahme eines Fremdtextes (inkl. aller dort zu findenden Literaturreferenzen) ohne jede Kennzeichnung.

Sichter
(Graf Isolan), SleepyHollow02

[2.] Shg/Fragment 017 15 - Diskussion
Zuletzt bearbeitet: 2014-11-01 21:20:28 Hindemith
BauernOpfer, Fragment, Gesichtet, Papadopoulou et al 2009, SMWFragment, Schutzlevel sysop, Shg

Typus
BauernOpfer
Bearbeiter
SleepyHollow02
Gesichtet
Yes.png
Untersuchte Arbeit:
Seite: 17, Zeilen: 15-34
Quelle: Papadopoulou et al 2009
Seite(n): 57, Zeilen: left col., 18 ff.
In prostate cancer, expression of mAR in human tumor cells was initially reported in iAR positive LNCaP cells [Kampa M, et al 2002] and iAR –deficient DU145 cells [Hatzoglou A, et al 2005]. In LNCaP cells study, mAR activation through testosterone-BSA conjugates induced rapid PSA release, fast actin reorganization and additional cell responses like inhibition of cell growth and induction of apoptosis [Hatzoglou A, et al 2005]. The molecular signaling pathway starts from focal adhesion kinase (FAK). Initially, FAK was rapidly phosphorylated and associated with the p85 subunit of the phosphoinositol-3-Kinase (PI-3K). Following this association, the lipid kinase activity of PI-3K and the tyrosine phosphorylation of its p85 regulatory subunit were significantly induced by mAR stimulation. PI-3K activation was accompanied by the downstream upregulation of the Rho small GTPases Cdc42, Rac1, RhoA and RhoB. Rapid activation of these GTPases resulted in actin cytoskeleton reorganization. Yet again, these effects were specific for mAR because three different steroidal and non-steroidal iAR antagonists failed to block the activation of this rapid signaling pathway [Papakonstanti, E. A., et al. 2003]. From these findings it was concluded that mAR activation induced potent apoptotic regression in LNCaP prostate tumor cells controlled by [Rho/ROCK/actin signaling.]

Kampa M, Papakonstanti EA, Hatzoglou A, Stathopoulos EN, Stournaras C, Castanas E. (2002). The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors that increase PSA secretion and modify actin cytoskeleton. Faseb J, 16:1429-1431.

Hatzoglou A, Kampa M, Kogia C, Charalampopoulos I, Theodoropoulos PA, Anezinis P, Dambaki C, Papakonstanti EA, Stathopoulos EN, Stournaras C, et al. (2005). Membrane androgen receptor activation induces apoptotic regression of human prostate cancer cells in vitro and in vivo. J Clin Endocrinol Metab, 90: 893-903.

Papakonstanti, E. A., Kampa, M., Castanas, E., and Stournaras, C. (2003). A rapid, nongenomic, signaling pathway regulates the actin reorganization induced by activation of membrane testosterone receptors. Mol. Endocrinol. 17, 870–881.

Expression of mAR in human tumor cells was initially reported in iAR positive LNCaP cells (9). In this study, mAR activation through testosterone, dihydrotestosterone (DHT) or TBSA conjugates induced rapid PSA release and potent and fast actin reorganization. Subsequent studies analyzed additional cell responses triggered by mAR stimulation including mAR-dependent inhibition of cell growth and induction of apoptosis (21). [...] Analysis of the molecular signaling activated by mAR identified a novel mAR-specific non-genomic pathway operating in LNCaP cells (25, 34). Initially, focal adhesion kinase (FAK) was rapidly phosphorylated and associated with the p85 subunit of the phosphoinositol-3-Kinase (PI-3K). Following this association, the lipid kinase activity of PI-3K and the tyrosine phosphorylation of its p85 regulatory subunit were significantly induced by mAR stimulation. PI-3K activation was accompanied by the downstream upregulation of the Rho small GTPases Cdc42, Rac1, RhoA and RhoB. Rapid activation of these GTPases resulted in actin cytoskeleton reorganization. Yet again, these effects were specific for mAR because three different steroidal and non-steroidal iAR antagonists failed to block the activation of this rapid signaling pathway (25). [...] From these findings it was concluded that mAR activation induces potent apoptotic regression in LNCaP prostate tumor cells controlled by Rho/ROCK/actin signaling.

9. Kampa, M., Papakonstanti, E. A., Hatzoglou, A., Stathopoulos, E. N., Stournaras, C., and Castanas, E. (2002) The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors that increase PSA secretion and modify actin cytoskeleton. Faseb. J. 16, 1429–1431.

21. Hatzoglou, A., Kampa, M., Kogia, C., Charalampopoulos, I., Theodoropoulos, P. A., Anezinis, P., Dambaki, C., Papakonstanti, E. A., Stathopoulos, E. A., Stournaras, C., Gravanis, A., and Castanas E. (2005) Membrane androgen receptor activation induces apoptotic regression of human prostate cancer cells in vitro and in vivo. J. Clin. Endocrinol. Metab. 90, 893–903.

25. Papakonstanti, E. A., Kampa, M., Castanas, E., and Stournaras, C. (2003) A rapid, nongenomic, signaling pathway regulates the actin reorganization induced by activation of membrane testosterone receptors. Mol. Endocrinol. 17, 870–881.

34. Papadopoulou, N., Charalampopoulos, I., Alevizopoulos, K., Gravanis, A., and Stournaras, C. 2008. Rho/ROCK/Actin signaling regualtes membrane androgen receptor induced apoptosis in prostate cancer cells. Exp. Cell. Res., 314, 3162–3174.

Anmerkungen

The source is given on the next page as reference for a figure.

Sichter
(SleepyHollow02), Hindemith


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