MITOSTATIN, a putative tumor suppressor on chromosome 12q24.1, is downregulated in human bladder and breast cancer

A. Vecchione, M. Fassan, V. Anesti, A. Morrione, S. Goldoni, G. Baldassarre, D. Byrne, D. D'Arca, J. P. Palazzo, J. Lloyd, L. Scorrano, L. G. Gomella, R. V. Iozzo, R. Baffa

Research output: Contribution to journalArticlepeer-review

Abstract

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a ∼62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in ∼5 and ∼11% of various cancer-derived cells and solid tumors, respectively. When transiently overexpressed, MITOSTATIN inhibited colony formation, tumor cell growth and was proapoptotic, all features shared by established tumor suppressor genes. We discovered a specific link between MITOSTATIN overexpression and downregulation of Hsp27. Conversely, MITOSTATIN knockdown cells showed an increase in cell growth and cell survival rates. Finally, MITOSTATIN expression was significantly reduced in primary bladder and breast tumors, and its reduction was associated with advanced tumor stages. Our findings support the hypothesis that MITOSTATIN has many hallmarks of a classical tumor suppressor in solid tumors and may play an important role in cancer development and progression.

Original languageEnglish
Pages (from-to)257-269
Number of pages13
JournalOncogene
Volume28
Issue number2
DOIs
Publication statusPublished - Jan 15 2009

Keywords

  • Bladder cancer
  • Breast cancer
  • Chromosome 12q
  • Mitochondria
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint

Dive into the research topics of 'MITOSTATIN, a putative tumor suppressor on chromosome 12q24.1, is downregulated in human bladder and breast cancer'. Together they form a unique fingerprint.

Cite this