K-ras 4A and 4B are co-expressed widely in human tissues, and their ratio is altered in sporadic colorectal cancer

S J Plowman, R L Berry, S A Bader, F Luo, M J Arends, D J Harrison, M L Hooper, C E Patek

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

Ras activating mutations result in constitutive activation of Ras signalling pathways and occur in 30% of human malignancies. K-ras encodes two splice variants, K-ras 4A and 4B, and K-ras activating mutations which jointly affect both isoforms are prevalent in lung, pancreatic and colorectal cancers. Using RT-PCR we examined their expression in normal adult human tissues and addressed whether K-ras splicing is altered in sporadic colorectal cancer by comparing normal colon with colon carcinoma cell lines, and 'matched' tumour and tumour-free colon tissues from the same patient. K-ras 4B was expressed ubiquitously and was the predominant splice variant. K-ras 4A was expressed differentially, with detection in colorectal tumours and cell lines, and normal colon, pancreas and lung--sites where tumours with K-ras activating mutations arise. Both K-ras splice variants were co-expressed by single colon carcinoma cells. The K-ras 4A/4B ratio was significantly reduced in all 6 cell lines examined, including two that lacked K-ras activating mutations, and in 4/9 primary adenocarcinomas. We conclude that K-ras activating mutations do not affect K-ras splicing per se, both isoforms may play a role in neoplastic progression, and altered splicing of either the K-ras proto-oncogene or oncogene, in favour of K-ras 4B, may modulate tumour development.
Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalJournal of Experimental & Clinical Cancer Research
Volume25
Issue number2
Publication statusPublished - Jun 2006

Keywords

  • Adenocarcinoma
  • Colon
  • Colorectal neoplasms
  • DNA mutational analysis
  • Genes, Ras
  • Humans
  • Mutation
  • Protein Isoforms
  • RNA, Messenger
  • Tumor cells, cultured

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