Annexin II expression is reduced or lost in prostate cancer cells and its re-expression inhibits prostate cancer cell migration.
While studying Bim, a BH3-only proapoptotic protein, we identified an approximately 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 approximately 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 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.
Liu
Jun-Wei
JW
Department of Carcinogenesis, The Uniersity of Texas MD Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957, USA.
Shen
Jian-Jun
JJ
Tanzillo-Swarts
Angela
A
Bhatia
Bobby
B
Maldonado
Carlos M
CM
Person
Maria D
MD
Lau
Serrine S
SS
Tang
Dean G
DG
D000595:Amino Acid Sequence; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D003600:Cytosol / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012016:Reference Values; D014407:Tumor Cells, Cultured
D017305:Annexin A1; D017306:Annexin A2; D002118:Calcium