RT Journal Article
T1 Bcl-xL is overexpressed in hormone-resistant prostate cancer and promotes survival of LNCaP cells via interaction with proapoptotic Bak.
A1 Castilla, Carolina
A1 Congregado, Belén
A1 Chinchón, David
A1 Torrubia, Francisco J
A1 Japón, Miguel A
A1 Sáez, Carmen
K1 Antineoplásicos Fitogénicos
K1 Apoptosis
K1 Camptotecina
K1 Línea Celular Tumoral
K1 Resistencia a Antineoplásicos
K1 Regulación Neoplásica de la Expresión Génica
K1 Humanos
K1 Inmunohistoquímica
K1 Masculino
K1 Fenotipo
K1 Neoplasias de la Próstata
K1 Proteína Destructora del Antagonista Homólogo bcl-2
K1 Proteína X Asociada a bcl-2
K1 Proteína bcl-X
K1 Antineoplásicos Hormonales
AB Androgen-sensitive prostate cancer cells turn androgen resistant through complex mechanisms that involve dysregulation of apoptosis. We investigated the role of antiapoptotic Bcl-xL in the progression of prostate cancer as well as the interactions of Bcl-xL with proapoptotic Bax and Bak in androgen-dependent and -independent prostate cancer cells. Immunohistochemical analysis was used to study the expression of Bcl-xL in a series of 139 prostate carcinomas and its association with Gleason grade and time to hormone resistance. Expression of Bcl-xL was more abundant in prostate carcinomas of higher Gleason grades and significantly associated with the onset of hormone-refractory disease. In vivo interactions of Bcl-xL with Bax or Bak in untreated and camptothecin-treated LNCaP and PC3 cells were investigated by means of coimmunoprecipitation. In the absence of any stimuli, Bcl-xL interacts with Bax and Bak in androgen-independent PC3 cells but only with Bak in androgen-dependent LNCaP cells. Interactions of Bcl-xL with Bax and Bak were also evidenced in lysates from high-grade prostate cancer tissues. In LNCaP cells treated with camptothecin, an inhibitor of topoisomerase I, the interaction between Bcl-xL and Bak was absent after 36 h, Bcl-xL decreased gradually and Bak increased coincidentally with the progress of apoptosis. These results support a model in which Bcl-xL would exert an inhibitory effect over Bak via heterodimerization. We propose that these interactions may provide mechanisms for suppressing the activity of proapoptotic Bax and Bak in prostate cancer cells and that Bcl-xL expression contributes to androgen resistance and progression of prostate cancer.
PB Endocrine Society
SN 0013-7227
YR 2006
FD 2006-10-10
LK http://hdl.handle.net/10668/1801
UL http://hdl.handle.net/10668/1801
LA en
NO Castilla C, Congregado B, Chinchón D, Torrubia FJ, Japón MA, Sáez C. Bcl-xL is overexpressed in hormone-resistant prostate cancer and promotes survival of LNCaP cells via interaction with proapoptotic Bak. Endocrinology. 2006; 147(10):4960-7
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 11, 2025