In mammary epithelial cells there are al least two pathways which promote apoptosis: one is activated by DNA damage and requires p53, the other which is p53-independent is induced in confluent cultures by growth factor withdrawal. In this publication we have examined p53-mediated, DNA damage-induced apoptosis in MCF10A human mammary epithelial cells which express wild-type p53. In cells treated with the DNA damage-inducing agents, mitomycin C, 5-Fluorouracil, cisplatin and u.v. irradiation, there is an increase in the levels of the p53 protein and the p21(CIP1/WAF1) cyclin-dependent kinase inhibitor. However, the ability of the agents to induce a cell cycle arrest or an apoptotic response varied considerably. Treatment with u.v. induced the highest level of apoptosis without an apparent effect on the cell cycle, whereas 5-Fluorouracil-treated cells showed a G1 arrest with no apoptosis. Mitomycin C treatment led to a moderate G1 arrest and a moderate level of apoptosis which could be increased in growth factor-starved cells. MCF10A cells expressed high levels of Bax, a death-promoting member of the Bcl-2 family. Bax expression was not influenced by treatments which promoted apoptosis. The results showed that the response of mammary epithelial cells to DNA damage is complex, dependent upon the inducing agent and can be influenced by culture conditions.
|Autori:||Merlo GR; Fiore L; Basolo F; WoodsCook K; Hynes NE|
|Titolo:||In mammary epithelial cells p53-mediated apoptosis in response to DNA damage is dependent on the agent and can be influenced by growth factors|
|Anno del prodotto:||1997|
|Appare nelle tipologie:||1.1 Articolo in rivista|