The retinoblastoma gene functions as a growth and tumor suppressor in human bladder carcinoma cells

Rei Takahashi, Tomoko Hashimoto, Hong Ji Xu, Shi Xu Hu, Toshimitsu Matsui, Toru Miki, Hélène Bigo-Marshall, Stuart A. Aaronson, William F. Benedict

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176 Scopus citations


The product of the human retinoblastoma gene (RB) is a nuclear phosphoprotein that is thought to function as a tumor suppressor. Mutations of RB frequently occur in human bladder carcinoma. To investigate the significance of the functional loss of this gene in bladder cancer, an RB expression plasmid (pBARB) under control of the human β-actin promoter was transfected into the bladder carcinoma cell line HTB9, which lacks RB expression. Marker-selected transfectants that expressed RB protein were identified by immunoblotting and immunohistochemical staining. In selected clones, stable RB expression has persisted over 1 yr under standard culture conditions with 10% serum. However, RB expression caused major alterations of HTB9 growth properties both in vitro and in vivo. RB+ transfectants lacked the ability to form colonies in semi-solid medium, and their growth rate was significantly decreased in 3% serum. In addition, the tumorigenicity of these transfectants was markedly decreased. Tumors that formed in nude mice were much smaller and had a longer latency period but were indistinguishable microscopically from those produced by parental cells. Slower growing tumors were RB+, as measured by nuclear staining of their RB protein and by a normal RB protein pattern on immunoblots. These findings support the concept that the RB gene acts as both a growth and tumor suppressor in bladder cancer cells.

Original languageEnglish
Pages (from-to)5257-5261
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - 15 Jun 1991
Externally publishedYes


  • Antioncogene
  • Gene transfection
  • Growth regulation
  • Tumorigenicity


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