Annexin 1 regulates cell proliferation by disruption of cell morphology and inhibition of cyclin D1 expression through sustained activation of the ERK1/2 MAPK signal

Annexin-1 Regulates Growth Arrest Induced by High Levels of Estrogen in MCF-7 Breast Cancer Cells

“…This suggests that ANXA1 is inherently an antiproliferative protein up-regulated to counter the overactivation of proliferative signals induced by 17h-E. This is similar to previous studies where ANXA1 was shown to regulate the proliferation of RAW macrophages (11) and mediated steroid-induced growth arrest in lung cancer cells (21). We have shown in this study that ANXA1 siRNAtransfected cells are unable to sustain prolonged ERK1/2 activation after 72 h when treated with high 17h-E doses, suggesting that ANXA1 is required for constitutive ERK1/2 activation observed in cells treated with high 17h-E concentrations over a prolonged period.…”

“…A low ANXA1 expression was shown to induce a prolonged stimulation of the mitogen-activated protein kinase pathway and subsequent increased cell proliferation in RAW macrophages (39); an overexpression of ANXA1 led to a constitutively sustained stimulation of the same pathway via activation of ERK1/2 and was accompanied by a reduction in cell proliferation due to an up-regulation of cell cycle arrest proteins such as p21 waf/cip (11). In our study, Western blot analyses showed that treatment of the cells with high concentrations of 17h-E induced ERK1/2 activation that was sustained even after 72 h, unlike treatment with lower concentrations of 17h-E, which resulted in an ERK1/2 activation that was not sustained.…”

“…4; for a review, see ref. 6) through the modulation of mitogen-activated protein kinase signaling, calcium ion mobilization, apoptosis (5), cell proliferation (8,9), and inhibition of cell growth (10,11).…”

An overview of the effects of annexin 1 on cells involved in the inflammatory process

“…Similar studies using stably transfected RAW 264.7 murine macrophages, showed that over-expression of ANXA1 results in constitutive activation of Erk, but not other related MAP kinases, P38 and c-Jun N-terminal kinase resulting in an inhibition of cellular proliferation (Alldridge et al 1999). These effects were shown to occur via disruption of the actin cytoskeleton and involved the adaptor protein Grb-2 in the ANXA1-mediated effect on Erk activation (Alldridge et al 2003).…”

Prognostic Significance of Annexin A1 Expression in Pancreatic Ductal Adenocarcinoma

“…Moreover, kim et al proposed that PMA-induced translocation of annexin A1 to the nucleus may participate in the regulation of cell proliferation and differentiation (Kim et al, 2003). In addition, several studied have approved that nuclear translocation of annexin A1 is involved in the regulation of cellular proliferation (Alldridge & Bryant., 2003;Alves et al, 2008). Similarly, in our study, as the tumor tissues of PDAC patients with high expression of annexin A1 and weak nuclear staining showed worse prognosis and outcome, we hypothesisd that annexin A1 translocated to the nuclei may be involved in the different processes in both cytoplasm and nuclei including specific cellular functions as well as signal transduction and the regulatory effects of annexin A1 may involve both transcriptional and translational levels.…”