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 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.

• Authors: Leonardo Vinícius Monteiro de Assis, Mauro César Isoldi
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 35 Issue 2 Pg. 889-901 (Feb 2014) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 24081673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Carcinogens
• Membrane Proteins
• TP53 protein, human
• Tumor Suppressor Protein p53
• Asbestos
• TPTE protein, human
• PTEN Phosphohydrolase

Topics

• Asbestos (toxicity)
• Carcinogens (toxicity)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lung Neoplasms (chemically induced, genetics, pathology, virology)
• Membrane Proteins (genetics, metabolism)
• Mesothelioma (chemically induced, genetics, pathology, virology)
• Mesothelioma, Malignant
• PTEN Phosphohydrolase (genetics, metabolism)
• Simian virus 40 (pathogenicity)
• Tumor Suppressor Protein p53 (genetics, metabolism)