Unknown

Dataset Information

0

C-Myc alters the DNA damage-induced G2/M arrest in human mammary epithelial cells.


ABSTRACT: Effects of c-Myc overexpression on the DNA damage-induced G2/M checkpoint were studied in finite lifespan, normal human mammary epithelial cells (HMECs). Previously, we showed that c-Myc attenuates G1/S arrest and leads to an inappropriate entry of cells with damaged DNA into the S phase, following treatment with ionising radiation (IR). Here we show that, in striking contrast to control cells, c-Myc-overexpressing HMECs demonstrate a significant attenuation of the G2/M arrest, following IR, and enter into inappropriate mitoses. At the molecular level, ectopic overexpression of c-Myc leads to an unusually high level of expression of cyclin B1, and the elevated levels of cyclin B1 were maintained, after gamma-irradiation. Introduction of DNA damage in c-Myc-overexpressing, normal mammary epithelial cells eventually induces apoptosis, indicating a dramatic sensitisation by c-Myc of DNA damage-induced apoptosis. These two remarkable phenotypes, checkpoint attenuation and sensitisation to apoptosis, resulting from a deregulation of the protooncogene c-myc, may produce a unique pattern of alternating cycles, consisting first of amplification of DNA damage, followed by apoptosis-assisted selective pressure. The result of this alternating pattern of damage apoptosis could facilitate the selection of certain genomic alterations required for cellular survival and cellular transformation.

SUBMITTER: Sheen JH 

PROVIDER: S-EPMC2394331 | biostudies-other | 2003 Oct

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC5341517 | biostudies-literature
| S-EPMC3047812 | biostudies-literature
| S-EPMC2892325 | biostudies-literature
| S-EPMC7070093 | biostudies-literature
| S-EPMC4381605 | biostudies-literature
| S-EPMC2663934 | biostudies-literature
| S-EPMC1489101 | biostudies-literature
| S-EPMC3913755 | biostudies-literature
| S-EPMC7154561 | biostudies-literature
| S-EPMC4873197 | biostudies-literature