Expression of Bcl-xL in ovarian carcinoma is associated with chemoresistance and recurrent disease.

Abstract:

OBJECTIVE:The long-term survival of patients with epithelial ovarian cancer is limited by the emergence of tumor cells that are resistant to chemotherapy. We hypothesized that expression of Bcl-x(L), a homologue of Bcl-2 that confers protection from chemotherapy-induced apoptosis, may be predictive of patients' clinical response to treatment, and that treatment with chemotherapy may result in the selection of tumor cells that overexpress this protein. METHODS:We determined the expression of Bcl-x(L) in epithelial ovarian cancers from 28 patients at the time of initial staging laparotomy and in recurrent tumors in the same patients following treatment with platinum-based chemotherapy. The data were analyzed to determine whether Bcl-x(L) expression was predictive of clinical outcome. A2780 ovarian cancer cells were stably transfected with Bcl-x(L) or control plasmid. Chemotherapy-induced apoptosis in these cell lines was determined in vitro and in a xenograft model. RESULTS:Bcl-x(L) expression in primary tumors was associated with a significantly shorter disease-free interval as compared to patients whose tumors did not express Bcl-x(L) (1.6 months as compared to 7.7 months). We found that Bcl-x(L) expression conferred resistance to chemotherapy-induced apoptosis resulting from treatment with cisplatin, paclitaxel, topotecan, and gemcitabine in vitro. In a xenograft model, Bcl-x(L) expressing tumors continued to grow following treatment with cisplatin, paclitaxel, topotecan, and gemcitabine, in contrast to control tumors, which disappeared. CONCLUSION:These results portray an important role for Bcl-x(L) as a key factor associated with chemotherapy failure in the treatment of ovarian cancer.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Williams J,Lucas PC,Griffith KA,Choi M,Fogoros S,Hu YY,Liu JR

doi

10.1016/j.ygyno.2004.10.026

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

287-95

issue

2

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(04)00828-5

journal_volume

96

pub_type

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