Cyclin D1 overexpression enhances radiation-induced apoptosis and radiosensitivity in a breast tumor cell line

Overexpression of cyclin D1, a G(1) cell cycle regulator, is often found in many different tumor types, such as breast carcinoma and squamous cell car cinoma of the head and neck. The overexpression of this protein is, in seve ral cases, associated with a poor prognosis. In this study, the effect of c yclin D1 on radiosensitivity was investigated in a breast tumor cell line, MCF7. containing a cyclin D1 gene construct under the control of a tetracyc line-sensitive regulator. MCF7 cells cultured without tetracycline resulted in a 6-fold increase in the cyclin D1 protein. Cyclin D1-overexpressing MCF7 cells were more sensitive to ionizing radiati on than the nonoverexpressing counterparts. The cyclin D1-overexpressing te lls also exhibited a higher induction of apoptosis. Treatment with a dose o f 5 Gy resulted in a rapid increase of p53 and p21 in the cyclin D1-overexp ressing cells. Nonoverexpressing cells showed a more transient expression o f these proteins after ionizing radiation. A pronounced G(2)-M block was ob served in both cell lines. The cyclin D1-overexpressing cells were, however , released earlier from the block than the control cells. These data suggest that overexpression of cyclin D1 alters sensitivity towa rd ionizing radiation by modulating gamma-radiation-induced G(2)-M transiti on.