Reprogramming of replicative senescence in hepatocellular carcinoma-derived cells.
basic_science · Level V
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- Record sourced from PubMed, PMID 16461895.
- Also identified by PMC identifier 1413736.
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Abstract
Tumor cells have the capacity to proliferate indefinitely that is qualified as replicative immortality. This ability contrasts with the intrinsic control of the number of cell divisions in human somatic tissues by a mechanism called replicative senescence. Replicative immortality is acquired by inactivation of p53 and p16INK4a genes and reactivation of hTERT gene expression. It is unknown whether the cancer cell replicative immortality is reversible. Here, we show the spontaneous induction of replicative senescence in p53-and p16INK4a-deficient hepatocellular carcinoma cells. This phenomenon is characterized with hTERT repression, telomere shortening, senescence arrest, and tumor suppression. SIP1 gene (ZFHX1B) is partly responsible for replicative senescence, because short hairpin RNA-mediated SIP1 inactivation released hTERT repression and rescued clonal hepatocellular carcinoma cells from senescence arrest.
Medical subject headings
- Carcinoma, Hepatocellular
- Cellular Senescence
- Cyclin-Dependent Kinase Inhibitor p16
- Homeodomain Proteins
- Liver Neoplasms
- Repressor Proteins
- Tumor Suppressor Protein p53