Korean J Urol.  2003 Feb;44(2):160-167.

Response of Human Renal Cell Carcinoma Cells to Bone Morphogenetic Proteins, and the Expression of Bone Morphogenetic Protein Receptors

• Lee DH
• Chung JH
• Kim IY

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.

Keyword

Bone morphogenetic protein (BMP); BMP receptor; Renal cell carcinoma

MeSH Terms

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
Bone Morphogenetic Protein 6
Bone Morphogenetic Protein Receptors
Bone Morphogenetic Proteins
Luciferases