Telomerase: cellular immortalization and neoplastic transformation. Multiple functions of a multifaceted complex.
The telomerase complex allows telomere length maintenance, which is required for an unlimited cellular proliferation. Telomerase is virtually absent in normal human somatic cells, which are characterized by a definite proliferation potential, while it is present in the vast majority of tumors (around 90%). Restoring telomerase activity in normal somatic cells can indefinitely prolong cellular life span. However, evidence has been reported that this event can be associated with the acquisition of characteristics typical of cellular transformation. Moreover, analysis of telomerase immortalized cells, as well as of tumor cells in which telomerase is inactivated, has highlighted multiple functions of telomerase in tumorigenesis, besides telomere lengthening. In this paper, we will review telomerase immortalization of somatic cells, together with its possible consequences, and we will examine the complex role of telomerase in tumorigenesis.
Belgiovine
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Istituto di Genetica Molecolare, CNR, Pavia, Italy.
Chiodi
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Mondello
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D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D005260:Female; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000648:ultrastructure
D021122:Protein Subunits; C509186:TERT protein, human; D019098:Telomerase