Regulation of telomerase and its hTERT messenger in colorectal cancer.
Telomeres are the distal ends of human chromosomes composed of tandem repeats of the sequence TTAGGG. In most human somatic cells, telomerase activity is undetectable, and the telomere length is progressively shortened during cell proliferation, leading to cellular senescence. In contrast, telomerase is activated in the vast majority of cancer cells, including colorectal cancer. The human telomerase complex is comprised of multiple components, but telomerase reverse transcriptase (hTERT) is the most important component for the control of telomerase activity. The p53 protein is a transcription factor with multiple biological activities, including cell cycle arrest and/or apoptosis upon DNA damage, hypoxia and oncogene activation; this requires transactivation or repression of specific target genes by wild-type p53. To better understand if a link between hTERT/telomerase regulation and p53 status exists in colorectal carcinogenesis, we analysed 43 cases of colorectal carcinoma for hTERT mRNA expression and telomerase activity. Moreover, a complete analysis of p53 status was performed. Alterations of p53 gene were found in 44.19% of cases and missense point mutations represented a high proportion of p53. Both telomerase activity (p=0.014) and hTERT expression (p=0.03) were significantly associated with p53 mutations, suggesting a role of p53 in the signaling pathway for telomerase control.
Boldrini
Laura
L
Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Via Roma 57, I-56126 Pisa, Italy.
Faviana
Pinuccia
P
Gisfredi
Silvia
S
Donati
Valentina
V
Zucconi
Ylenia
Y
Ursino
Silvia
S
Simi
Paolo
P
Baldinotti
Fulvia
F
Berti
Piero
P
Galleri
Davide
D
Materazzi
Gabriele
G
Basolo
Fulvio
F
Miccoli
Paolo
P
Pingitore
Raffaele
R
Fontanini
Gabriella
G
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000601:surgery; D019943:Amino Acid Substitution; D003062:Codon / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000601:surgery; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000601:surgery; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D019098:Telomerase / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D003062:Codon; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D019098:Telomerase