The mechanism of the growth-inhibitory effect of coxsackie and adenovirus receptor (CAR) on human bladder cancer: A functional analysis of car protein structure

T. Okegawa, R. C. Pong, Y. Li, J. M. Bergelson, Arthur I Sagalowsky, Jer-Tsong Hsieh

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

The coxsackie and adenovirus receptor (CAR) is identified as a high-affinity receptor for adenovirus type 5. We observed that invasive bladder cancer specimens had significantly reduced CAR mRNA levels compared with superficial bladder cancer specimens, which suggests that CAR may play a role in the progression of bladder cancer. Elevated CAR expression in the T24 cell line (CAR-negative cells) increased its sensitivity to adenovirus infection and significantly inhibited its in vitro growth, accompanied by p21 and hypophosphorylated retinoblastoma accumulation. Conversely, decreased CAR levels in both RT4 and 253J cell lines (CAR-positive cells) promoted their in vitro growth. To unveil the mechanism of action of CAR, we showed that the extracellular domain of CAR facilitated intercellular adhesion. Furthermore, interrupting intercellular adhesion of CAR by a specific antibody alleviates the growth-inhibitory effect of CAR. We also demonstrated that both the transmembrane and intracellular domains of CAR were critical for its growth-inhibitory activity. These data indicate that the cell-cell contact initiated by membrane-bound CAR can elicit a negative signal cascade to modulate cell cycle regulators inside the nucleus of bladder cancer cells. Therefore, the presence of CAR cannot only facilitate viral uptake of adenovirus but also inhibit cell growth. These results can be integrated to formulate a new strategy for bladder cancer therapy.

Original languageEnglish (US)
Pages (from-to)6592-6600
Number of pages9
JournalCancer Research
Volume61
Issue number17
StatePublished - Aug 1 2001

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Coxsackie and Adenovirus Receptor-Like Membrane Protein
Urinary Bladder Neoplasms
Growth
Proteins
Adenoviridae Infections
Cell Line
Retinoblastoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The mechanism of the growth-inhibitory effect of coxsackie and adenovirus receptor (CAR) on human bladder cancer : A functional analysis of car protein structure. / Okegawa, T.; Pong, R. C.; Li, Y.; Bergelson, J. M.; Sagalowsky, Arthur I; Hsieh, Jer-Tsong.

In: Cancer Research, Vol. 61, No. 17, 01.08.2001, p. 6592-6600.

Research output: Contribution to journalArticle

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