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Radio‐induced modulation of transforming growth factor β1 sensitivity in a p53 wild‐type human colorectal‐cancer cell line
Author(s) -
Suardet Laurent,
Li Chuan,
Little John B.
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960927)68:1<126::aid-ijc22>3.0.co;2-8
Subject(s) - radiosensitivity , radioresistance , radiation sensitivity , cell culture , cancer research , biology , ionizing radiation , transforming growth factor , growth inhibition , cell growth , medicine , irradiation , endocrinology , radiation therapy , genetics , physics , nuclear physics
Unlike normal intestinal cells, colorectal‐carcinoma cell lines are usually not responsive to transforming growth factor B1. The cyclin‐dependent kinase inhibitor p21 that is induced by X irradiation in cells expressing normal p53 can also be induced by TGF‐B1 by a p53 ‐independent pathway. We have investigated possible interactions between ionizing radiation and TGF‐B1, using a panel of 8 human colorectal‐cancer cell lines varying in p53 status and sensitivity to the cyto‐inhibitory effect of TGF‐B1. Heterogeneity in the radiosensitivity of these cell lines was observed, with SF 2 (surviving fraction after irradiation with 2 Gy) ranging from 0.19 to 0.82. Radioresistance (high SF 2 values) was in general associated with abnormal expression of p53 . An effect of TGF‐B1 treatment on radiosensitivity was observed with one cell line only (LS513), and manifested by enhancement of the cytotoxic effect of radiation. In an experiment with fractionated irradiation during continuous exposure to TGF‐B1, there was no change in the intrinsic radiosensitivity of LS513 cells, though irradiated cells treated with TGF‐B1 were more sensitive to the first radiation dose. Irradiated LS513 colorectal‐cancer and Mv‐I‐Lu epithelial cells were significantly more sensitive to TGF‐B1 than were unirradiated controls, whereas no change was observed in the TGF‐B1 sensitivity of irradiated LS1034 cells. Radio‐induced modulation of TGF‐B1 sensitivity was transitory and declined before the decline to baseline level of p21 mRNA expression. On the basis of these results, we postulate that radiation‐induced sensitization to TGF‐B1 occurs in TGF‐B1‐sensitive cells expressing wild‐type p53 . © 1996 Wiley‐Liss, Inc.