The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms

Abstract

The malignant mesothelioma is an aggressive form of cancer with a mean survival rate of less than a year. Moreover, environmental exposure to minerals is an important factor in the development of malignant mesothelioma (MM), especially the mineral asbestos, which has a well-documented role in MM, and more recently, the mineral erionite has been proven to be a strong carcinogenic inducer of MM. In addition, the virus simian virus 40 has been implicated as a co-carcinogenic player in MM. However, the molecular mechanisms involved in the pathogenesis of this cancer are still not fully understood. Indeed, it is known that several genes are altered or mutated in MM, among those are p16INK4A, p14ARF, and neurofibromatosis type II. Furthermore, TP53 has been reported to be mutated in the majority of the cancers; however, in MM, it is very uncommon mutations in this gene. Also, the PTEN gene has been shown to play an important role in endometrial cancer and glioblastoma, although the role of PTEN in MM has yet to be established. Taken altogether, this review focuses on the historical aspects, molecular mechanisms, interaction with other genes and proteins, and the role of these genes in MM. Lastly, this review questions the cancer theory of the two hits because the functions of both PTEN and TP53 are not fully explained by this theory.

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Acknowledgments

The authors thank Mark Pershouse, PhD, associate professor of the Department of Biomedical and Pharmaceutical Science at the University of Montana, USA, for his teachings, lessons, and mentoring Pablo Henrique Oliveira e Silva for revising this manuscript; Izabella Imperatriz Moreira Dalboni de Souza for creating and editing the figures present in this paper; CAPES for granting a 1-year scholarship to the first author of this paper at the University of Montana, USA; and CNPQ and Fundação de Amparo à Pesquisa do estado de Minas Gerais (FAPEMIG) for the financial support given to our Laboratory at the Federal University of Ouro Preto.

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Correspondence to Mauro César Isoldi.

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de Assis, L.V.M., Isoldi, M.C. The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms. Tumor Biol. 35, 889–901 (2014). https://doi.org/10.1007/s13277-013-1210-4

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Keywords

  • Mesothelioma
  • PTEN
  • p53
  • Asbestos
  • PI3K/AKT
  • Quasi-sufficiency and haploinsufficiency genes