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Typus
Verschleierung
Bearbeiter
SleepyHollow02
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Untersuchte Arbeit:
Seite: 78, Zeilen: 3-24
Quelle: Gu et al 2009
Seite(n): 12, Zeilen: l.col: 32ff
5.2 Membrane androgen receptor activation blocks migration

The connection between actin cytoskeleton components and androgen signaling has attracted specific interest in recent years [Ting HJ, et al. 2008]. Actin dynamics seem to be crucial for apoptotic responses [Gourlay CW, et al.2005, Franklin-Tong VE, et al.2008]. The findings in our present work further underscored the key role of actin cytoskeleton rearrangements in regulating apoptosis. Indeed, it was clearly shown that actin (and tubulin) reorganization represent major early events following mAR activation by testosterone-HSA. Moreover, early blockade of actin rearrangement by depolymerizing drugs e.g. cytochalasin B, virtually abrogated the pro-apoptotic responses (Fig. 15A, B). The involvement of the early actin rearrangement in mediating the late apoptotic responses was addressed in earlier studies in prostate cancer cells. In these studies it was shown that inhibition of either up-stream or down-stream signals regulating early actin polymerization blocked the late activation of NFkB and FasL signaling [Papadopoulou N, et al. 2008A]. Although this pro-apoptotic signaling was not addressed in the present study we hypothesise that the actin reorganization is an early functional step in the pro-apoptotic response. These findings, which are in close agreement with similar results reported recently in prostate cancer cells treated with testosterone albumin conjugates [Papadopoulou N, et al. 2008 and 2008A], further emphasize the functional cross-talk between cytoskeleton rearrangements and regulation of apoptosis [Gourlay CW, et al.2005, Franklin-Tong VE, et al.2008].


Gourlay CW, Ayscough KR. (2005).The actin cytoskeleton: a key regulator of apoptosis and ageing? Nat. Rev. Mol. Cell. Biol, 6(7):6583-589.

Franklin-Tong VE, Gourlay CW. (2008). A role for actin in regulating apoptosis/programmed cell death: evidence spanning yeast, plants and animals. Biochem J. 413(3):389-404.

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.

The connection between actin cytoskeleton components and androgen signaling has attracted specific interest in recent years (for a review see [36]). Actin dynamics seem to be crucial for apoptotic responses [28,29]. The findings in our present work further underscored the key role of actin cytoskeleton rearrangements in regulating apoptosis. Indeed, it was clearly shown that actin (and tubulin) reorganization represent major early events following mAR activation by testosterone-HSA. Moreover, early blockade of actin rearrangement by depolymerizing drugs e.g. cytochalasin B, virtually abrogated the pro-apoptotic responses (Fig. 5A, B). The involvement of the early actin rearrangement in mediating the late apoptotic responses was addressed in earlier studies in prostate cancer cells. In these studies it was shown that inhibition of either upstream or down-stream signals regulating early actin polymerization blocked the late activation of NF-κB and FasL signaling [9]. Although the pro-apoptotic signaling was not addressed in the present study we hypothesize that the actin reorganization is an early functional step in the pro-apoptotic response. These findings, which are in close agreement with similar results reported recently in prostate cancer cells treated with testosterone albumin conjugates [8,9], further emphasize the functional crosstalk between cytoskeleton rearrangements and regulation of apoptosis [28,29].

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 downregulation 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

28. Gourlay CW, Ayscough KR: The actin cytoskeleton: a key regulator of apoptosis and ageing? Nat Rev Mol Cell Biol 2005, 6(7):6583-589.

29. Franklin-Tong VE, Gourlay CW: A role for actin in regulating apoptosis/programmed cell death: evidence spanning yeast, plants and animals. Biochem J 2008, 413(3):389-404.

36. Ting HJ, Chang C: Actin associated proteins function as androgen receptor coregulators: an implication of androgen receptor's roles in skeletal muscle. J Steroid Biochem Mol Biol 2008, 111(3-5):157-163

Anmerkungen

Die Quelle Ting hat Shg zwar zitiert, aber vergessen im Quellenverzeichnis aufzulisten.

Man beachte die Anmerkung zur Quelle Gu et al. (2009)

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