Abstract
While studying Bim, a BH3-only proapoptotic protein, we identified an ∼36 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 ∼36 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 Ca2+ 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.
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Abbreviations
- 2D-PAGE:
-
two-dimensional polyacrylamide gel electrophoresis
- aa:
-
amino acids
- BrdU:
-
5-bromo-2′-deoxyuridine
- DAPI:
-
4′, 6-diamidino-2-phenylindole
- hrGFP:
-
humanized Renilla green fluorescence protein
- MALDI-TOF:
-
matrix-assisted laser desorption/ionization time of flight
- MS:
-
mass spectrometry
- NHP:
-
normal human prostate epithelial cells
- PSD:
-
postsource decay
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Acknowledgements
We thank C Conti for providing C4-2, C5, and MDA2b cells, D Chopra for NHP2 and NHP5 cells, and S Krishnan for assisting in MALDI-TOF analysis. This work was supported, in part, by the National Institute of Health Grants CA-90297 (DGT) and GM39338 (SSL), NIEHS Center Grant ES07784 (JJS, DGT, MDP, SSL), and MDACC institutional grants (DGT).
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Liu, JW., Shen, JJ., Tanzillo-Swarts, A. et al. Annexin II expression is reduced or lost in prostate cancer cells and its re-expression inhibits prostate cancer cell migration. Oncogene 22, 1475–1485 (2003). https://doi.org/10.1038/sj.onc.1206196
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DOI: https://doi.org/10.1038/sj.onc.1206196
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