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

Our plain-English summary of 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, by L.V. de Assis, M.C. Isoldi (Tumour Biology, 2014).

The study

• Authors: L.V. de Assis, M.C. Isoldi
• Journal: Tumour Biology
• Published: 2014;35(2):889-901
• Type of article: Review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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 p16(INK4A), p14(ARF), 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.

In plain English

This article was a narrative review, not a new study. It summarized published research on malignant mesothelioma, on asbestos and how it may cause the disease, and on two genes, PTEN and TP53, including how they work and interact and what is known about them in mesothelioma. The review described asbestos as serpentine (chrysotile) and amphibole (crocidolite, amosite, anthophyllite, actinolite, tremolite). It noted a continuing debate over whether chrysotile causes mesothelioma. Citing earlier studies, it reported that TP53 mutation is uncommon in mesothelioma. It also reported that studies of PTEN disagreed: one study of 341 mesothelioma samples found PTEN expression lost in 62% of cases, while other studies found loss less often. A protective mechanism linking PTEN and p53 had been shown only in animals. The authors argued that PTEN and TP53 are not fully explained by the classic two-hit theory of cancer. They concluded that the roles of PTEN and p53 in mesothelioma remain open to debate. They suggested reducing exposure to asbestos and other minerals through prohibition or restrictive laws.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published literature (no original data; no search method described)
• Who was studied: No study population; the review covered published laboratory, animal and human research on malignant mesothelioma and on the genes PTEN and TP53
• Exposure: Asbestos in general: serpentine (chrysotile) and amphiboles (crocidolite, amosite, anthophyllite, actinolite, tremolite). Erionite and simian virus 40 (SV40) were also discussed as other factors. The review described crocidolite as the most oncogenic and chrysotile as the least.
• Main results:
  • Citing earlier studies, the review stated that mutation of TP53 is uncommon in mesothelioma
  • Earlier studies of PTEN in mesothelioma disagreed.
• In one cited study of 63 patients, 19 tumors could be analyzed, and 16% of these showed no PTEN expression.
• In 21 mesothelioma cell lines, two showed no PTEN expression.
• In 86 samples, 26.7% showed no expression and 26.7% weak expression.
• In 341 samples, PTEN expression was lost in 62%, and this loss was correlated with worse survival.
  • The review stated that the PTEN–p53 cross-talk mechanisms it described (PTEN loss-induced cellular senescence, and aggressive cancer when PTEN loss is combined with mutant TP53) had been demonstrated only in animals
  • The review stated that whether chrysotile causes mesothelioma is still debated and inconclusive, because of discrepancies in the literature
  • Citing earlier evidence, the review stated that 80% of individuals diagnosed with mesothelioma had previous asbestos exposure
  • Citing a Brazilian mortality study, the review reported that the mesothelioma death rate in Brazil was 0.68 per million people in 1980 and 1.01 in 2003
  • The review described TP53 as a classic exception to the two-hit theory (haploinsufficiency). It described PTEN as a quasi-sufficiency gene, for which even a small decrease in expression influenced cancer development in mice.
• The authors' conclusion: The authors concluded that the roles of PTEN and p53 in mesothelioma are still open to debate and that better understanding of these pathways is needed for new drugs or prevention. Because current treatments are not very effective, they suggested reducing exposure to asbestos and other minerals through prohibition or restrictive laws.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Environmental Exposure, erionite, Carcinogenic.

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• Exploratory analysis of activation of PTEN-PI3K pathway and downstream proteins in malignant pleural mesothelioma (MPM) — S. Cedrés, M.A. Montero, et al. (2012)
• Analysis of expression of PTEN/PI3K pathway and programmed cell death ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM) — S. Cedrés, S. Ponce-Aix, et al. (2016)
• First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications — M.W. Löffler, J. Steinhilber, et al. (2018)
• The diagnostic role of PTEN and ARID1A in serous effusions — B. Davidson, M. Pinamonti, et al. (2018)
• Connecting molecular pathways to hereditary cancer risk syndromes — J.R. Testa, D. Malkin, et al. (2013)

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