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Quelle: Papadopoulou et al 2009 Seite(n): 58, Zeilen: left col., 3 ff. |
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| [Solid arrows] indicate events that have been experimentally proven. Dashed arrows indicate unidentified possible links. See text for details. [Papadopoulou N, et al 2009]
In breast cancer, it has been reported that mAR is expressed in T47D and MCF7 human breast epithelial cancer cells. In T47D cells, specific and saturable androgen receptors are present in the membrane and their activation via TBSA conjugates resultes [sic] in cell death by apoptosis. [Kampa M, et al 2005] Moreover, pharmacological inhibitors of MEK and p38 kinase were able to block T-BSA induced apoptosis showing a functional implication of these pathways in mAR-dependent apoptosis in T47D cells. However, in MCF7 cells, activation of these receptors by T-BSA conjugates triggered a non-genomic signaling pathway involving FAK and PI-3K phosphorylation and downstream activation of the small GTPase Rac1, ultimately resulting in actin redistribution. Cell migration experiments provided insights in the functional role of mAR stimulation in MCF7 cells. But the activations of mAR did not induce any apoptotic response in this kind of cells. [Kallergi G, et a.l 2007]
Figure 4: mAR signaling in breast epithelial cancer cells Non-genomic mAR signaling operating in MCF7 breast epithelial cancer cells regulating actin redistribution and cell motility. Solid arrows indicate events that have been experimentally proven. Dashed arrows indicate unidentified possible links. [Papadopoulou N, et al 2009] Papadopoulou N, Papakonstanti EA, Kallergi G, Alevizopoulos K, Stournaras C. (2009). Membrane androgen receptor activation in prostate and breast tumor cells: Molecular signaling and clinical impact. IUBMB Life, 61(1): 56-61. Kampa M, Nifli AP, Charalampopoulos I, Alexaki VI, Theodoropoulos PA, Stathopoulos EN, Gravanis A, Castanas E. (2005). Opposing effects of estradiol- and testosterone-membrane binding sites on T47D breast cancer cell apoptosis. Exp Cell Res, 307:41-51. 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. |
Figure 2. Early and late mAR signaling operating in iAR deficient DU145 human prostate cancer cells regulating actin redistribution, downstream pro-apoptotic signaling, and migration. Solid arrows indicate events that have been experimentally proven. Dashed arrows indicate unidentified possible links. See text for details.
Figure 3. Non-genomic mAR signaling operating in MCF7 breast epithelial cancer cells regulating actin redistribution and cell motility. Solid arrows indicate events that have been experimentally proven. Dashed arrows indicate unidentified possible links. See text for details. Besides prostate cancer cells, mAR expression has recently been reported in T47D and MCF7 human breast epithelial cancer cells. In T47D cells, specific and saturable androgen receptors are present in the membrane and their activation via TBSA conjugates resulted in cell death by apoptosis (15). [...] Moreover, pharmacological inhibitors of MEK and p38 kinase were able to block T-BSA induced apoptosis showing a functional implication of these pathways in mAR-dependent apoptosis in T47D cells. In another recent study, we have reported the expression of mAR in MCF7 cells (20). Activation of these receptors by T-BSA conjugates triggered a non-genomic signaling pathway involving FAK and PI-3K phosphorylation and downstream activation of the small GTPase Rac1, ultimately resulting in actin redistribution. [...] Cell migration experiments provided insights in the functional role of mAR stimulation in MCF7 cells. [...]
15. Kampa, M., Nifli, A. P., Charalampopoulos, I., Alexaki, V. I., Theodoropoulos, P.A., Stathopoulos, E.N., Gravanis, A., and Castanas, E. (2005) Opposing effects of estradiol- and testosterone-membrane binding sites on T47D breast cancer cell apoptosis. Exp. Cell. Res. 307, 41–51. 20. Kallergi, G., Agelaki, S., Markomanolaki, H., Georgoulias, V., and 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. |
Although the source is given for the figure nothing has been marked as a citation. |
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