Telomerase expression in lung preneoplasia and neoplasia.
Telomeres are specialized structures at eukaryotic chromosomes ends, which role is to prevent them from degradation, end to-end fusion and rearrangement. However, they shorten after each cellular division because of an incomplete DNA replication, acting in normal somatic cells as a mitotic clock for permanent proliferation arrest or senescence entry. Short telomeres are perceived as damaged DNA leading to p53/ATM pathway activation. In tumoral cells, a ribonucleoprotein complex termed telomerase enables telomere elongation. This complex, composed of 2 main components, the telomerase RNA component or hTR, the RNA template for telomere synthesis, and telomerase reverse transcriptase, the catalytic subunit, is reactivated in the majority of cancers, including those of the lung. In this review, we briefly present the main results on telomerase expression in various histological types of lung carcinoma and in bronchial carcinogenesis along with telomere attrition. Inhibition of one of the main components of the enzyme or limitation of telomere access by telomerase represent novel targets for cancer therapies and chemoprevention in high risk patients of lung cancer.
Lantuéjoul
Sylvie
S
Department of Pathology and Lung Cancer Research Group INSERM U 578, Institut A Bonniot, CHU Michallon, Grenoble, France.
Salon
Caroline
C
Soria
Jean-Charles
JC
Brambilla
Elisabeth
E
D004789:Enzyme Activation; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics; D011230:Precancerous Conditions / Q000201:enzymology* / Q000235:genetics; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D016615:Telomere
D019098:Telomerase