TY - JOUR
T1 - Down-regulation of homeobox gene GBX2 expression inhibits human prostate cancer clonogenic ability and tumorigenicity
AU - Gao, Allen C.
AU - Lou, Wei
AU - Isaacs, John T.
PY - 1998/4/1
Y1 - 1998/4/1
N2 - Previously, we have demonstrated that GBX genes, a homeobox-containing human family of DNA-binding transcription factors consisting of GBX1 and GBX2, are overexpressed in a panel of human prostatic cancer cell lines (i.e., TSU-pr1, PC3, DU145, and LNCaP) compared to normal prostate. In the present studies, specific primer sets were designed for reverse transcription-PCR detection of the expression of GBX1 versus GBX2 in human prostate cancer. These studies demonstrated that the GBX2 gene, but not the GBX1 gene, is consistently overexpressed in this panel of human prostate cancer cell lines compared to normal human prostate. Using a quantitative- competitive PCR analysis, GBX2 mRNA was expressed as 3 x 103 copies/μg RNA in normal prostate tissue and 4 x 104 copies/μg RNA in the immortalized normal neonatal prostate epithelial cell line 267B-1, as compared to 6 x 105, 5 x 105, 3 x 105, and 1 x 105 copies/μg RNA in TSU-pr1, DU145, LNCaP, and PC3 prostate cancer cell lines, respectively. To examine the importance of GBX2 expression for prostate cancer malignancy, GBX2- overexpressing TSU-pr1 and PC3 human prostatic cancer cells were transfected with a eukaryotic expression vector containing an antisense GBX2 homeobox domain cDNA. Stable transfectant clones with 5-10-told decreased levels of GBX2 mRNA expression were obtained. When tested in vitro, the clonogenic ability of the GBX2 antisense transfectants was reduced by approximately 50% in both cell lines. When implanted s.c. into nude mice, the tumorigenicity of the antisense GBX2 transfectants from both human prostatic cancer cell lines was inhibited by more than 70% compared to the parental cells. These results suggest that expression of GBX2 gene is required for malignant growth of human prostate cells.
AB - Previously, we have demonstrated that GBX genes, a homeobox-containing human family of DNA-binding transcription factors consisting of GBX1 and GBX2, are overexpressed in a panel of human prostatic cancer cell lines (i.e., TSU-pr1, PC3, DU145, and LNCaP) compared to normal prostate. In the present studies, specific primer sets were designed for reverse transcription-PCR detection of the expression of GBX1 versus GBX2 in human prostate cancer. These studies demonstrated that the GBX2 gene, but not the GBX1 gene, is consistently overexpressed in this panel of human prostate cancer cell lines compared to normal human prostate. Using a quantitative- competitive PCR analysis, GBX2 mRNA was expressed as 3 x 103 copies/μg RNA in normal prostate tissue and 4 x 104 copies/μg RNA in the immortalized normal neonatal prostate epithelial cell line 267B-1, as compared to 6 x 105, 5 x 105, 3 x 105, and 1 x 105 copies/μg RNA in TSU-pr1, DU145, LNCaP, and PC3 prostate cancer cell lines, respectively. To examine the importance of GBX2 expression for prostate cancer malignancy, GBX2- overexpressing TSU-pr1 and PC3 human prostatic cancer cells were transfected with a eukaryotic expression vector containing an antisense GBX2 homeobox domain cDNA. Stable transfectant clones with 5-10-told decreased levels of GBX2 mRNA expression were obtained. When tested in vitro, the clonogenic ability of the GBX2 antisense transfectants was reduced by approximately 50% in both cell lines. When implanted s.c. into nude mice, the tumorigenicity of the antisense GBX2 transfectants from both human prostatic cancer cell lines was inhibited by more than 70% compared to the parental cells. These results suggest that expression of GBX2 gene is required for malignant growth of human prostate cells.
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M3 - Article
C2 - 9537237
AN - SCOPUS:0032053817
SN - 0008-5472
VL - 58
SP - 1391
EP - 1394
JO - Cancer Research
JF - Cancer Research
IS - 7
ER -