Reciprocal relationship between the tumor suppressors p53 and BAX in primary colorectal cancers

Lisa A. Simms, Graham Radford-Smith, Kelli G. Biden, Ron Buttenshaw, Margaret Cummings, Jeremy R. Jass, Joanne Young, Stephen J. Meltzer, Barbara A. Leggett

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Though most colorectal cancers show allelic losses, a subset of colorectal cancers (microsatellite instability or MSI-positive cancers) develop numerous small insertion and deletion mutations in repetitive DNA. Some of these sequences occur in coding regions of cancer related genes which, when targeted by frameshift mutations, produce truncations in their protein product, Such a gene is the proapoptotic tumor suppressor, BAX, mutated by frameshifts within a polyG sequence in approximately 50% of MSI-positive colorectal cancers. BAX is directly transactivated by p53, a gene commonly mutated in colorectal cancers but not often in MSI-positive lesions. Here we sought to characterize the relationship between BAX and p53 by simultaneously analysing a selected series of 65 colorectal tumors for mutations in the entire coding regions of both genes. The tumors comprised 19 MSI-high, 12 MSI-low and 34 MSI-null cancers. Eight of 19 MSI-high sporadic colorectal cancers (42%) contained insertions and deletions at the polyG tract in the BAX gene. In addition, three somatic BAX missense mutations mere identified in two tumors. A single missense mutation was detected in an MSI-high tumor that also contained a frameshift microdeletion, and two missense mutations were identified in an MSI-null tumor wild-type for p53. p53 mutations were detected in 5/12 MSI-low tumors (42%) and 12/34 MSI-null tumors (35%). Of significance, no p53 mutations were detected in MSI-high tumors. This study demonstrates that a reciprocal relationship exists between p53 and BAX in sporadic colorectal cancers, and further supports the hypothesis that MSI-low tumors are biologically similar to MSI-null tumors.

Original languageEnglish (US)
Pages (from-to)2003-2008
Number of pages6
Issue number15
StatePublished - Oct 15 1998
Externally publishedYes


  • BAX
  • Colorectal cancer
  • Microsatellite instability
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


Dive into the research topics of 'Reciprocal relationship between the tumor suppressors p53 and BAX in primary colorectal cancers'. Together they form a unique fingerprint.

Cite this