Telomerase in human development and cancer.

A potentially rate-limiting step in cancer progression is the conversion of a normal human cell into one capable of indefinite proliferation. There are at least two different cellular mechanisms that must be overcome before immortalization occurs. The first step generally requires inactivation of the pathways involving two tumor-suppressor genes, p53 and pRB, and the second step almost always involves the reactivation of the ribonucleoprotein enzyme telomerase. Telomerase synthesizes hexameric repeats (TTAGGG) onto telomeric ends, thereby compensating for telomeric losses that in its absence occurs at each cell division. Telomerase is present in human embryonic tissues, is not detected in most adult tissues, but is upregulated or reactivated in almost 90% of all human cancers. In the present article, I review the telomere-telomerase theory of aging and cancer including the roles of telomerase during human development, in differentiation, and in cancer. Research into the regulation of this enzyme may lead to methods to facilitate the accurate diagnosis of cancer and to the development of novel antitelomerase cancer therapeutics.