Abstract |
Insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1) has been shown to have decreased expression in the progression from benign to malignant prostate epithelial cells (V. Hwa et al., J. Clin Endocrinol. Metab., 83: 4355-4362, 1998). The present study was undertaken to determine the effects of the re-expression of IGFBP-rP1 in a cell line from a model of human prostate cancer, M12, in which IGFBP-rP1 expression had been demonstrated to decrease from the parent epithelial cell, P69, to the malignant subline, M12. An IGFBP-rP1 cDNA encoding the protein was transfected into M12 cells in a plasmid that resulted in constitutive-expression of IGFBP-rP1. Clones of transfected M12 cells were selected for low (L) and high (H) levels of expression, and the plasmid vector alone was transfected into M12 as a control. After transfection, there was a marked alteration in the morphology of the M12 cells such that the H clones had an elongated appearance when compared with the M12 control cells. The M12 clones overexpressing IGFBP-rP1 had a dose-related increase in population doubling time, decreased colony formation in soft agar, an increased propensity to undergo apoptosis in response to 6-hydroxyurea, and decreased tumor formation in male athymic, nude mice. These data suggest that IGFBP-rP1 may have a suppressive effect on prostate cancer development.
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Authors | C C Sprenger, S E Damon, V Hwa, R G Rosenfeld, S R Plymate |
Journal | Cancer research
(Cancer Res)
Vol. 59
Issue 10
Pg. 2370-5
(May 15 1999)
ISSN: 0008-5472 [Print] United States |
PMID | 10344746
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Carrier Proteins
- DNA, Complementary
- Insulin-Like Growth Factor Binding Proteins
- Neoplasm Proteins
- Recombinant Fusion Proteins
- insulin-like growth factor binding protein-related protein 1
- Hydroxyurea
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Topics |
- Animals
- Apoptosis
(drug effects)
- Carrier Proteins
(biosynthesis, genetics, physiology)
- Cell Division
- Cell Size
- DNA, Complementary
(genetics)
- Genes, Tumor Suppressor
- Humans
- Hydroxyurea
(pharmacology)
- Insulin-Like Growth Factor Binding Proteins
(biosynthesis, genetics, physiology)
- Male
- Mice
- Mice, Nude
- Neoplasm Proteins
(biosynthesis, genetics, physiology)
- Neoplasm Transplantation
- Prostatic Neoplasms
(genetics, pathology)
- Recombinant Fusion Proteins
(physiology)
- Transfection
- Tumor Cells, Cultured
- Tumor Stem Cell Assay
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