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- W2897853339 abstract "550 Previously, we reported the isolation of a novel gene located on chromosome 1 in Epidermal Differentiation Complex (EDC) which encodes a 146 amino acids transmembrane protein that we called Prostate Androgen Regulated (PAR) gene. The PAR gene is expressed as a single mRNA species in all normal tissues studied and is over expressed in majority of tumors, including breast and prostate. The modulation of PAR expression induced by transfection with gene encoding sequence in sense and antisense orientation suggests that PAR is a protooncogene. Here we report the effect of anti P1 (PAR) antibodies on proliferation of MCF 7 and DU 145 cancer cells. Anti P1 antibody is a highly specific, affinity purified rabbit polyclonal antibody raised against a 20 amino acid antigenic peptide (P1) selected from the amino terminal deduced PAR sequence. On Western blots this antibody reacted with P1 peptide, with recombinant PAR protein prepared in E coli, and with lysates from LNCaP and MCF 7 cells, but not with BSA or protein standards. Antibody activity was completely abolished by antibody pre treatment with P1 peptide indicating its specificity. In tissue culture this antibody induced inhibition of cell proliferation of DU 145 and MCF 7 cells in a dose and time dependent manner. At a concentration of 9 μg/ml about 90% of MCF 7 cells were dead within 4-5 days compared with the control cells treated with IgG from normal rabbits. MCF 10F normal breast cells were not affected by the same treatment. When given ip twice a week in dose of 50 μg/mouse the anti P1 antibody significantly inhibited the growth of DU 145 cells tumors in CB17 SCID mice. Anti PAR antibody induced apoptosis in DU145 cells as evidenced by flow cytometric detection of sub-G1 DNA content. This apoptotic process was associated with down-regulation of Bcl-2 and an increase of caspase-3 activity. Further work is carried out in our laboratory to determine the mechanism of antiproliferative effect of these antibodies." @default.
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- W2897853339 date "2005-05-01" @default.
- W2897853339 modified "2023-09-23" @default.
- W2897853339 title "Antiproliferative effect of anti PAR antibody on breast and prostate cancer cells" @default.
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