Estrogens exert multiple effects on target cells probably related to various action mechanisms which start after hormone binding to both estrogen receptor isoforms (ER and ER 17-estradiol (E2)-induced rapid/non genomic signal transduction pathways (i.e., AKT and ERK phosphorylation) are both necessary and sufficient to mediate G1-S phase transition in several target cells. Here, the ability of the two ER isoforms to activate different signal transduction pathways and to drive cells into or out of the cell cycle has been analyzed. HeLa cells, devoid of any endogenous ER, have been used as experimental model after the transient transfection with expression vectors encoding for human ER or ER. The results show that E2 induces target gene promoter activity in HeLa cells only after transfection with ER or ER. Furthermore, E2 increases the number of ER-transfected HeLa cells in the G1 phase of the cell cycle. On the contrary, in the presence of ER, E2 decreases the cellular population in the G1 phase of the cell cycle and increases the number of cells in sub-G1 phase, a marker of DNA fragmentation. These data are consistent with the ability of E2 to trigger both caspase-3 activation and the cleavage of PARP in ER-expressing HeLa cells. The role played by signal transduction pathways shows that the E2-ER complex does not activate any of the E2-ER-activated signal molecules involved in cell growth (i.e., AKT and ERK). However, in the presence of ER, E2 induces a persistent phosphorylation of MAPK/p38 which is involved in both the regulation of caspase-3 activation and the cleavage of PARP. On the other hand, in the presence of ER, the E2-dependent MAPK/p38 activation is transient. Taken together, these results demonstrate the ability of ER isoform to activate specific signal transduction pathways starting from plasma membrane that may justify the effect of E2 in inducing cell proliferation or apoptosis in cancer cells. In particular this hormone promotes cell survival through ER non-genomic signalling and cell death through ER non-genomic signalling.
Acconcia, F., Galluzzo, P., Trentalance, A., Marino, M. (2006). DIVERGENT PROLIFERATIVE ESTRADIOL EFFECTS: ROLE OF ERalpha AND ERbeta RAPID SIGNALS, 188 sup.652, 165.
DIVERGENT PROLIFERATIVE ESTRADIOL EFFECTS: ROLE OF ERalpha AND ERbeta RAPID SIGNALS
ACCONCIA, FILIPPO;GALLUZZO, PAOLA;TRENTALANCE, Anna;MARINO, Maria
2006-01-01
Abstract
Estrogens exert multiple effects on target cells probably related to various action mechanisms which start after hormone binding to both estrogen receptor isoforms (ER and ER 17-estradiol (E2)-induced rapid/non genomic signal transduction pathways (i.e., AKT and ERK phosphorylation) are both necessary and sufficient to mediate G1-S phase transition in several target cells. Here, the ability of the two ER isoforms to activate different signal transduction pathways and to drive cells into or out of the cell cycle has been analyzed. HeLa cells, devoid of any endogenous ER, have been used as experimental model after the transient transfection with expression vectors encoding for human ER or ER. The results show that E2 induces target gene promoter activity in HeLa cells only after transfection with ER or ER. Furthermore, E2 increases the number of ER-transfected HeLa cells in the G1 phase of the cell cycle. On the contrary, in the presence of ER, E2 decreases the cellular population in the G1 phase of the cell cycle and increases the number of cells in sub-G1 phase, a marker of DNA fragmentation. These data are consistent with the ability of E2 to trigger both caspase-3 activation and the cleavage of PARP in ER-expressing HeLa cells. The role played by signal transduction pathways shows that the E2-ER complex does not activate any of the E2-ER-activated signal molecules involved in cell growth (i.e., AKT and ERK). However, in the presence of ER, E2 induces a persistent phosphorylation of MAPK/p38 which is involved in both the regulation of caspase-3 activation and the cleavage of PARP. On the other hand, in the presence of ER, the E2-dependent MAPK/p38 activation is transient. Taken together, these results demonstrate the ability of ER isoform to activate specific signal transduction pathways starting from plasma membrane that may justify the effect of E2 in inducing cell proliferation or apoptosis in cancer cells. In particular this hormone promotes cell survival through ER non-genomic signalling and cell death through ER non-genomic signalling.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
