Mitochondrial Cytochrome B gene mutation promotes tumor growth in bladder cancer

Santanu Dasgupta, Mohammad Hoque, Sunil Upadhyay, David Sidransky

Research output: Contribution to journalArticle

Abstract

Mitochondria-encoded Cytochrome B (CYTB) gene mutations were reported in different cancers, but the effect of these mutations on cellular metabolism and growth is unknown. In a murine xenograft and human model of bladder cancer, we show the functional effect of overexpression of a 21-bp deletion mutation (mt) of CYTB. Overexpression of mtCYTB generated increased reactive oxygen species (ROS) accompanied by increased oxygen consumption and lactate production. MtCYTB overexpression induced significant tumor growth in vitro and in vivo by triggering rapid cell cycle progression through up-regulation of the nuclear factor-κB2 signaling pathway. Tumor-generated ROS induced in vitro lysis of normal splenocytes. Thus, we present physiologic and functional evidence for the role of a bonafide mitochondrial gene mutation in cancer.

Original languageEnglish (US)
Pages (from-to)700-706
Number of pages7
JournalCancer Research
Volume68
Issue number3
DOIs
StatePublished - Feb 1 2008

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Cytochromes
Urinary Bladder Neoplasms
Mutation
Growth
Genes
Reactive Oxygen Species
Neoplasms
Mitochondrial Genes
Sequence Deletion
Heterografts
Oxygen Consumption
Lactic Acid
Cell Cycle
Mitochondria
Up-Regulation
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mitochondrial Cytochrome B gene mutation promotes tumor growth in bladder cancer. / Dasgupta, Santanu; Hoque, Mohammad; Upadhyay, Sunil; Sidransky, David.

In: Cancer Research, Vol. 68, No. 3, 01.02.2008, p. 700-706.

Research output: Contribution to journalArticle

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