| | |  | | | | Record from Web of Science® | | | | | | |
| Cell cycle arrest defect in Li-Fraumeni Syndrome: A mechanism of cancer predisposition? |
|
|
| Author(s): Williams KJ, Boyle JM, Birch JM, Norton JD, Scott D |
| Source: ONCOGENE Volume: 14 Issue: 3 Pages: 277-282 Published: JAN 23 1997 |
| Times Cited: 31 References: 35 |
| Abstract: Cancer predisposition in approximately 60% of Li-Fraumeni Syndrome (LPS) families is associated with germline mutation of the TP53 gene. The p53 protein has been shown to mediate G(1) arrest following DNA damage, We have investigated gamma-irradiation-induced transient and permanent G(1) arrest in normal and LFS fibroblasts. The duration of transient G(1) arrest varied between strains, but there was no difference in the range between normal (2-12 h) and LFS (1-13 h) cells. However, the extent of permanent G(1) arrest was greatly reduced in LFS fibroblasts (mean 33 +/- 8% of the cell population) compared with normals (mean 67 +/- 9%) and correlated with their increased radiation survival (r = 0.97, P<0.001). This phenotype was observed in LFS fibroblasts both with (seven cases) and without (two cases) TP53 mutation. Parallel studies with fibroblasts derived from cancer-prone, p53-deficient mice revealed no radiation-induced G(1) cell cycle arrest in p53 null (-/-) cells, The p53 +/- cells were comparable to the wt p53 cells in transient G(1) arrest capacity, but showed a diminished permanent G(1) arrest. These data clearly implicate p53 function in permanent G(1) arrest, The reduced capacity for DNA damage-induced, permanent G(1) arrest in LFS may contribute significantly to cancer predisposition in this familial syndrome. |
| Document Type: Article |
| Language: English |
| Reprint Address: Williams, KJ (reprint author), CHRISTIE HOSP NHS TRUST, CRC, DEPT CANC GENET, PATERSON INST CANC RES, MANCHESTER M20 9BX, LANCS ENGLAND |
Addresses:
1. CHRISTIE HOSP NHS TRUST, CRC, PAEDIAT & FAMILIAL CANC RES GRP, PATERSON INST CANC RES, MANCHESTER M20 9BX, LANCS ENGLAND
2. CHRISTIE HOSP NHS TRUST, CRC, DEPT GENE REGULAT, PATERSON INST CANC RES, MANCHESTER M20 9BX, LANCS ENGLAND |
| Publisher: STOCKTON PRESS, HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS |
| Subject Category: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity |
| IDS Number: WD516 |
| ISSN: 0950-9232 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |