Endothelial p21(WAF1/CiP1) cell cycle inhibitor is down-regulated in breast cancer.
BACKGROUND
Tumor angiogenesis is considered a multi-pathway process, while p21(WAF1/CiP1) is a CDK inhibitor involved in cell division and survivaL Herein the tumor environment effect on endothelial p21(WAF1/Cip1) expression is examined.


METHODS
The EA.hy 926 endothelial cell line and tumor-conditioned medium (TCM) from the MDA-MB-468 breast cancer cell line were used. Endothelial cells grown alone and in TCM were immunostained for p21(WAF1/Cip1) and analyzed by RT-PCR Forty-four cases of breast cancer and forty-three cases of normal breast tissue were immunostained for p21(WAF1/Cip1).


RESULTS
Endothelial p21(WAF1/Cip1) is transcriptionally down-regulated under the influence of TCM. Moreover, it seems that breast cancer tumor endothelium does not express p21(WAF1/Cip1).


CONCLUSIONS
P21(WAF1/Cip1) plays a major role in angiogenesis, since tumor cells seem to down-regulate endothelial p21(WAF1/Cip1), compared to endothelial cells grown in serum-free medium. The verification of the tissue culture experiment results by immunohistochemistry on tissue sections indicates p21(WAF1/Cip1) as a target of modern molecular therapy.
Vrekoussis
T
T
Department of General Surgery, University Hospital and Medical School University of Crete, Heraklion, Greece.
Stathopoulos
E N
EN
Kafousi
M
M
Saridaki
Z
Z
Sanidas
E
E
Zoras
O
O
D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D048708:Cell Growth Processes / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D017077:Culture Media, Conditioned; D050759:Cyclin-Dependent Kinase Inhibitor p21