TY - JOUR
T1 - Inhibition of growth of cervical cancer cells using a dominant negative estrogen receptor gene
AU - Au, William W.
AU - Abdou-Salama, Salama
AU - Al-Hendy, Ayman
N1 - Funding Information:
The study is partially supported by grants from the John Sealy Memorial Foundation to W.W. Au, NIEHS pilot project grant #ES06676 to S.A.S. and NICHD grant R01-HD 46228 to A.A.
PY - 2007/2
Y1 - 2007/2
N2 - Objective.: Estrogen stimulates human papilloma virus oncogene expression, promotes cervical cancer (CC) cell proliferation and prevents apoptosis. Therefore, blockage of estrogen function may have therapeutic application to CC. Methods.: CasKi CC cells were transfected with an adenovirus expressing a dominant negative estrogen receptor gene (Ad-ER-DN) and their responses were investigated by RT-PCR, Flow Cytometry and Western blot assays. Result.: Transfected cells showed disturbance of cell colony morphology, reduced HPV E6 and E7 mRNA, interruption of cell proliferation, reduced cyclin D1 protein and expression of apoptosis. Conclusion.: We report, for the first time, the use of Ad-ER-DN to block estrogen receptors which led to dramatic changes in CC cells that are consistent with the possible reactivation of cellular p53 and Rb function. Their reactivation most likely allowed the recognition of existing chromosome abnormalities as a serious stress signal and the initiation of a cascade of cellular events in response to the stress, including the activation of the core apoptotic machinery which led to self-destruction of the CC cells.
AB - Objective.: Estrogen stimulates human papilloma virus oncogene expression, promotes cervical cancer (CC) cell proliferation and prevents apoptosis. Therefore, blockage of estrogen function may have therapeutic application to CC. Methods.: CasKi CC cells were transfected with an adenovirus expressing a dominant negative estrogen receptor gene (Ad-ER-DN) and their responses were investigated by RT-PCR, Flow Cytometry and Western blot assays. Result.: Transfected cells showed disturbance of cell colony morphology, reduced HPV E6 and E7 mRNA, interruption of cell proliferation, reduced cyclin D1 protein and expression of apoptosis. Conclusion.: We report, for the first time, the use of Ad-ER-DN to block estrogen receptors which led to dramatic changes in CC cells that are consistent with the possible reactivation of cellular p53 and Rb function. Their reactivation most likely allowed the recognition of existing chromosome abnormalities as a serious stress signal and the initiation of a cascade of cellular events in response to the stress, including the activation of the core apoptotic machinery which led to self-destruction of the CC cells.
KW - Cervical cancer
KW - Cyclin D1
KW - Dominant negative estrogen receptor gene
KW - Estrogen
KW - Estrogen receptor
KW - Gene therapy
KW - HPV
KW - Molecular intervention
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U2 - 10.1016/j.ygyno.2006.10.015
DO - 10.1016/j.ygyno.2006.10.015
M3 - Article
C2 - 17137618
AN - SCOPUS:33846377598
SN - 0090-8258
VL - 104
SP - 276
EP - 280
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -