Deregulated expression of c-mos in non-small cell lung carcinomas: relationship with p53 status, genomic instability, and tumor kinetics

V G Gorgoulis, P Zacharatos, G Mariatos, T Liloglou, S Kokotas, N Kastrinakis, A Kotsinas, A Athanasiou, P Foukas, V Zoumpourlis, D Kletsas, J Ikonomopoulos, P J Asimacopoulos, C Kittas, J K Field

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38 Citations (Scopus)


Little is known about the status of the mitogen-activating protein kinase pathways in lung cancer. One of the key molecules taking part in these pathways is the product of the c-mos proto-oncogene, which plays an important role in oocyte maturation. In vitro investigations in somatic cells have shown that c-mos expression has opposing effects on the cell cycle, which suggests that this proto-oncogene may represent an important determinant of aberrant cell function (genomic instability and altered kinetics). A recent study suggests that these effects may be p53 dependent. In view of the apparent link between c-mos and p53, we investigated in a series of 56 non-small cell lung carcinomas: a) the status of c-mos; b) its relationship to genomic instability (aneuploidy) and two kinetic parameters of the tumors, proliferation and apoptotic indexes (AI); and c) its association with p53 alterations and their concomitant relationship with the above parameters. We found c-mos overexpression in 27% of the tumors. Expression was higher in stages II/III (34%) than in stage I (17%; P = 0.018). Complete concordance was observed between c-mos overexpression and elevated c-mos mRNA levels. Because c-mos gene amplification was not detected, its deregulated expression may be attributable to increased transcription. Of the c-mos positive [c-mos(P)] cases, 77% were associated with aneuploidy. Sequencing showed two silent mutations and one missense (R-->L) at codon 22, located in a region critical for c-mos stability. In contrast to the findings of some in vitro studies, c-mos(P) tumors had a lower mean AI score than the c-mos negative [c-mos(N)] tumors had, implying that induction of apoptosis may have been defective. Indeed, 86% of the tumors overexpressing c-mos showed p53 alterations. The carcinomas with concomitant alterations of c-mos and p53 [c-mos(P)/p53 positive] had significantly lower AI values (P < 0.001) and were more frequently associated with aneuploidy (P = 0.015) than the c-mos(N)/p53 negative tumors but not the c-mos(N)/p53 positive tumors, which suggests that p53 status is the main determinant of ploidy status and apoptosis in our series. This finding also strengthens the concept that wild-type p53 plays a "safeguard" role in preventing oncogene-mediated activation.

Original languageEnglish
Pages (from-to)538-49
Number of pages12
JournalCancer Research
Issue number2
Publication statusPublished - 15 Jan 2001


  • Aged
  • Aneuploidy
  • Apoptosis
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung/genetics
  • Cell Division
  • DNA Mutational Analysis
  • DNA, Neoplasm/chemistry
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms/genetics
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinases/metabolism
  • Mutation
  • Neoplasm Staging
  • Phosphorylation
  • Polymorphism, Single-Stranded Conformational
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-mos/genetics
  • RNA, Messenger/genetics
  • Survival Analysis
  • Tumor Suppressor Protein p53/genetics


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