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Stable lower PAR expression decreased DU145 prostate cancer cell growth in SCID mice
Author(s) -
Platica Micsunica,
Ivan Elena,
Chen Sheryl,
Holland James F.,
Gil Juan,
Mandeli John,
Platica Ovidiu
Publication year - 2001
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.1135
Subject(s) - du145 , flow cytometry , cell cycle , biology , cell growth , transfection , microbiology and biotechnology , cell , mitosis , cancer research , cell culture , prostate cancer , pathology , cancer , medicine , lncap , genetics
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. Prostate 49:200–207, 2001. © 2001 Wiley‐Liss, Inc.