Annexin II expression is reduced or lost in prostate cancer cells and its re-expression inhibits prostate cancer cell migration

Abstract

While studying Bim, a BH3-only proapoptotic protein, we identified an B36 kDa protein, which was abundantly expressed in all five strains of primary normal human prostate (NHP) epithelial cells but significantly reduced or lost in seven prostate cancer cell lines. The B36 kDa protein was subsequently identified as annexin II by proteomic approach and confirmed by Western blotting using an annexin II-specific antibody. Conventional and 2D SDS-PAGE, together with Western blotting, also revealed reduced or lost expression of annexin I in prostate cancer cells. Subcellular localization studies revealed that in NHP cells, annexin II was distributed both in the cytosol and underneath the plasma membrane, but not on the cell surface. Prostate cancer cells showed reduced levels as well as altered expression patterns of annexin II. Since annexins play important roles in maintaining Ca 2+ homeostasis and regulating the cytoskeleton and cell motility, we hypothesized that the reduced or lost expression of annexin I/II might promote certain aggressive phenotypes of prostate cancer cells. In subsequent experiments, we indeed observed that restoration of annexin II expression inhibited the migration of the transfected prostate cancer cells without affecting cell proliferation or apoptosis. Hence, our results suggest that annexin II, and, likely, annexin I, may be endogenous suppressors of prostate cancer cell migration and their reduced or lost expression may contribute to prostate cancer development and progression.

Identification of Metal-binding Proteins in Human Hepatoma Lines by Immobilized Metal Affinity Chromatography and Mass Spectrometry

“…A pair of amino acid sequence repeats may form a composite binding site for a metal ion and a phospholipid in the structure of annexin II (58). Since expression of annexin II may be reduced or lost in prostate cancer cells in vivo (59,60), changes as we found in our studies may relate to neoplastic transformation in human hepatoma cells. Another important finding is the identification of a variable post-translational modification in the Cu-binding protein EF-1␣ by MS/MS measurements and homology protein database searching.…”

Annexin II represents metastatic potential in clear-cell renal cell carcinoma

“…Upregulation of ANX2 expression has been reported in hepatocellular carcinoma (Frohlich et al, 1990), lung cancer (Cole et al, 1992), pancreatic cancer (Diaz et al, 2004;Esposito et al, 2006), breast cancer (Sharma et al, 2006), gastrointestinal cancer (Singh, 2007), glioma (Reeves et al, 1992) and colorectal cancer (Emoto et al, 2001b). Conversely, downregulation of ANX2 expression has been reported in prostate cancer (Chetcuti et al, 2001;Banerjee et al, 2003;Liu et al, 2003), osteosarcoma (Gillette et al, 2004), oesophageal squamous cell carcinoma (SCC) (Zhi et al, 2003) and head and neck SCC (Pena-Alonso et al, 2008). This discrepancy may be explained by ANX2 expression in the histological origin of tumours, the cellular localisation and the putative function of ANX2 in tumour cells.…”

Differential tissue-specific protein markers of vaginal carcinoma

“…In renal carcinoma annexin 2 has been suggested as a useful prognostic marker (Zimmermann et al, 2004). However, reduced or lost expression of annexin 2 has been noticed in prostate carcinoma (Liu et al, 2003a) and osteosarcoma (Gillette et al, 2004) and has been related to aggressive behaviour and metastatic potential.…”