Untitled

Abstract

The protein-tyrosine kinase substrate annexin II is a growth regulated gene whose expression is increased in several human cancers. While the precise function of this protein is not understood, annexin II is proposed to be involved in multiple physiological activities, including DNA synthesis and cell proliferation. Targeted disruption of the annexin II gene affects calcium signaling, tyrosine phosphorylation and apoptosis, indicating the important physiological role of this protein. We used a transient co-transfection assay to regulate annexin II expression in human HeLa, 293 and 293T cells, and measured the effects of annexin II down regulation on DNA synthesis and proliferation. Transfection of cells with an antisense annexin II vector results in inhibition of cell division and proliferation, with concomitant reduction in annexin II message and protein levels. Cellular DNA synthesis is significantly reduced in antisense transfected cells. Replication extracts made from antisense transfected cells have significantly reduced efficiency to support SV40 in vitro DNA replication, while the extracts made from sense transfected cells are fully capable of replication. Our results indicate an important role of annexin II in cellular DNA synthesis and cell proliferation.

Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells

“…All these studies thus strongly suggest that ANX II is a key regulator of DNA synthesis and cell proliferation. Highaffinity binding sites for PG (ANX II) are present on colonic and intestinal epithelial cells Singh et al, 2003;Rengifo-Cam and Singh, 2004) and colon cancer cells (current studies), but are absent in the brain or liver (unpublished data from our laboratory), which agrees with the reported expression of ANX II (PG 'receptor'), primarily in proliferating cells (Frohlich et al, 1990;Chiang et al, 1993). Cellular functions of ANX II are regulated by posttranslational modifications and cellular localization.…”

Fetuin-A (α2HS-Glycoprotein) Is a Major Serum Adhesive Protein That Mediates Growth Signaling in Breast Tumor Cells

“…Interestingly, AnxA2 has been shown to promote cell spreading in intestinal epithelial cells (35), suggesting that the abilities of AnxA2 and AnxA6 to mediate cell spreading is cell type-dependent. It has been reported that down-regulation of AnxA2 expression in human cells markedly reduced their proliferation (36). The mechanism driving this AnxA2-based cell proliferation was not defined by this report.…”

Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis

“…Thus, Anx2 is associated with the regulation of DNA synthesis, and probably also with the cell cycle (Chiang et al, 1993) and cellular proliferation (Kumble et al, 1992b). Other functions include regulation of membrane trafficking such as exocytosis (Liu et al, 1996;Konig et al, 1998) and actin filament bundling (Jones et al, 1992), immunosuppression in RCC (Aarli et al, 1997) and insulin-induced signal transduction (Biener et al, 1996).…”