RRC ID |
12747
|
著者 |
Baba M, Hirai S, Kawakami S, Kishida T, Sakai N, Kaneko S, Yao M, Shuin T, Kubota Y, Hosaka M, Ohno S.
|
タイトル |
Tumor suppressor protein VHL is induced at high cell density and mediates contact inhibition of cell growth.
|
ジャーナル |
Oncogene
|
Abstract |
In spite of the general recognition of von Hippel-Lindau (VHL) as a tumor suppressor gene, the physiological and pathological importance of VHL protein in cell growth regulation and tumorigenesis remains unclear. Here we show that in normal human renal proximal tubule epithelial cells (RPTEC), the steady-state amount of VHL protein is strictly regulated by cell density. The cellular VHL content is more than 100-fold higher in dense cultures than in sparse cultures. The increase in VHL protein at high cell density was also observed for NIH3T3 fibroblasts, suggesting the generality of the phenomenon. The growth rates of renal cell carcinoma cells lacking an intact VHL gene and their derivatives with wild-type or mutant VHL expression vector do not differ significantly when they are growing in log-phase. Importantly, however, there is a difference when they reach confluency: cells lacking wild-type VHL grew continuously, while cells expressing exogenous VHL protein showed relatively limited cell growth. Using an ecdysone-inducible VHL expressing cell line, we also show that the growth inhibition at high cell density can be released by attenuating the VHL expression. Taken together, we propose that VHL protein functions as a growth suppressor at high cell density, and this might be the basis of the tumor suppressor function of VHL.
|
巻・号 |
20(22)
|
ページ |
2727-36
|
公開日 |
2001-5-17
|
DOI |
10.1038/sj.onc.1204397
|
PMID |
11420685
|
MeSH |
3T3 Cells / metabolism
3T3 Cells / pathology
Animals
Carcinoma, Renal Cell / metabolism
Carcinoma, Renal Cell / pathology
Cell Communication
Cell Count*
Cell Division
Cell Line
Genes, Tumor Suppressor*
Humans
Kidney Neoplasms / metabolism
Kidney Neoplasms / pathology
Kidney Tubules, Proximal / cytology*
Kidney Tubules, Proximal / metabolism*
Ligases*
Mice
Proteins / chemistry
Proteins / genetics
Proteins / metabolism*
Tumor Suppressor Proteins*
Ubiquitin-Protein Ligases*
Von Hippel-Lindau Tumor Suppressor Protein
|
IF |
7.971
|
引用数 |
38
|
WOS 分野
|
ONCOLOGY
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
遺伝子材料 |
pAxCAwt (RDB1678) |