Stable lower PAR expression decreased DU145 prostate cancer cell growth in SCID mice.
BACKGROUND
PAR is a novel gene ubiquitously expressed in normal and malignant tissues with a trend towards higher expression in tumor cells. PAR biological function is unknown. Here we report the effect of lowering PAR expression on in vitro and in vivo proliferation of DU145 cells.


METHODS
Decreased PAR expression was achieved by stable transfection of DU145 cells with antisense PAR cDNA cloned in pCMV-Script expression vector. The proliferative potential of DU145 transfectants was studied by cell counts, colony formation in soft agar, flow cytometry, and growth in severe combined immunodeficient (SCID) mice.


RESULTS
DU145 transfectants exhibited a decreased cell proliferation in tissue culture and a low efficiency of colony formation in soft agar. Flow cytometry revealed an arrest of these cells in G2-M phase of mitotic cycle. A dramatic decrease of tumor growth was observed when DU145 transfectant cells were inoculated in SCID mice, compared with controls. Histological examination of these tumors showed a marked decrease in cell density and in number of mitoses while control tumors showed a high cell density and numerous mitoses.


CONCLUSIONS
The data presented here provide the first evidence for PAR gene cellular function and its possible implication in malignant transformation.
Platica
M
M
Department of Medicine, Mount Sinai Medical Center, New York, New York 10029, USA. mickey.platica@mssm.edu
Ivan
E
E
Chen
S
S
Holland
J F
JF
Gil
J
J
Mandeli
J
J
Platica
O
O
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D016373:DNA, Antisense / Q000235:genetics / Q000494:pharmacology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D011994:Recombinant Proteins / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D014162:Transfection; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; C407989:JTB protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins