Response of Human Renal Cell Carcinoma Cells to Bone Morphogenetic Proteins, and the Expression of Bone Morphogenetic Protein Receptors.
- Author:
Dong Hyeon LEE
1
;
Jun Ho CHUNG
;
Isaac Yi KIM
Author Information
1. Departments of Urology, College of Medicine, Ewha Womans University, Seoul, Korea. leedohn@mm.ewha.ac.kr
- Publication Type:Original Article
- Keywords:
Bone morphogenetic protein (BMP);
BMP receptor;
Renal cell carcinoma
- MeSH:
Adenoviridae;
Adenoviridae Infections;
Blotting, Northern;
Bone Morphogenetic Protein 6;
Bone Morphogenetic Protein Receptors*;
Bone Morphogenetic Proteins*;
Carcinoma, Renal Cell*;
Cell Line;
Genes, Reporter;
Homeostasis;
Humans*;
Kidney;
Luciferases;
Transfection
- From:Korean Journal of Urology
2003;44(2):160-167
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Bone morphogenetic protein (BMP) is a pleiotropic growth factor, which has been suggested to play a critical role during the development and homeostasis of the kidney. We evaluated the response of the human renal cell carcinoma (RCC) cell lines to BMPs. MATERIALS AND METHODS: We evaluated the growth rate of the human RCC cell lines, 112, 117 and 181, according to the concentrations of BMP-4, -6 and -7, and detected the levels of the BMP receptors (BMPRs) expressed in the cell lines. To demonstrate that the defect in BMP-6 signaling is at the receptor level, BMP-6 resistant cell lines were transfected, with adenovirus containing the constitutively active form of the BMP receptor types II (BMPR-II). After transfection, the cells were transfected with pSBE4, the construct of the BMP-6-responsive luciferase reporter gene, and a luciferase assay performed. RESULTS: The BMP-6 inhibited the proliferation of the 112, but not those of the 117 and 181 cells, in a dose-dependent manner. From Northern blot and immunoblot analyses, it was demonstrated that the 117 and 181 cells had undetectable levels of BMPR-II expression. The levels of luciferase activity, following adenovirus infections, was elevated in both the 117 and 181 cells, suggesting that the down-stream signaling molecules of the BMP-6 was intact in these cell lines. CONCLUSIONS: Taken together, these results demonstrate that the human RCC cell lines 117 and 181 are resistant to the growth inhibitory effects of the BMP-6 due to their decreased levels of BMPR-II expression.
