TY - JOUR
T1 - Cyclin E-associated kinase activity predicts response to platinum-based chemotherapy
AU - Bedrosian, Isabelle
AU - Lee, Christine
AU - Tucker, Susan L.
AU - Palla, Shana L.
AU - Lu, Karen
AU - Keyomarsi, Khandan
PY - 2007/8/15
Y1 - 2007/8/15
N2 - Purpose: The role of cyclin E as a predictive marker of response to chemotherapy remains unknown. We have previously shown that deregulation of cyclin E in an ovarian tumor cell line model enhances cyclin E - associated kinase activity and sensitizes tumor cells to cisplatinum. We hypothesized that cyclin E deregulation would predict for responsiveness to platinum-based regimens in ovarian cancer patients. Experimental Design: Patients who met the following criteria were retrospectively identified from the institutional tumor bank records: (a) high-grade ovarian epithelial malignancy, (b) stage III/stage IV disease, (c) optimally debulked, (d) completed platinum-based therapy. Tumor samples were analyzed for cyclin E, p21, and p27 by Western blot analysis and assessed for cyclin E - associated kinase activity. Results: Seventy-five patients, who met the study criteria, were identified. Cyclin E protein levels did not correlate with cyclin E - cdk2 kinase activity (Spearman's rho, 0.07; P = 0.58). Cyclin E - associated kinase activity was the only significant predictive marker for response to platinum-based therapy, with higher response rates seen in patients with higher levels of activity (P = 0.045). Cyclin E protein levels did not predict for platinum sensitivity (P = 0.20). In contrast, cyclin E protein levels, but not cyclin E - associated kinase activity, was a significant predictor for freedom from recurrence (P = 0.01 and P = 0.25, respectively). Conclusions: Cyclin E overexpression and cyclin E - associated kinase activity have distinct roles in predicting for response to chemotherapy and outcome in ovarian cancer patients. These results suggest a compartmentalization of cyclin E functions in the oncogenic process.
AB - Purpose: The role of cyclin E as a predictive marker of response to chemotherapy remains unknown. We have previously shown that deregulation of cyclin E in an ovarian tumor cell line model enhances cyclin E - associated kinase activity and sensitizes tumor cells to cisplatinum. We hypothesized that cyclin E deregulation would predict for responsiveness to platinum-based regimens in ovarian cancer patients. Experimental Design: Patients who met the following criteria were retrospectively identified from the institutional tumor bank records: (a) high-grade ovarian epithelial malignancy, (b) stage III/stage IV disease, (c) optimally debulked, (d) completed platinum-based therapy. Tumor samples were analyzed for cyclin E, p21, and p27 by Western blot analysis and assessed for cyclin E - associated kinase activity. Results: Seventy-five patients, who met the study criteria, were identified. Cyclin E protein levels did not correlate with cyclin E - cdk2 kinase activity (Spearman's rho, 0.07; P = 0.58). Cyclin E - associated kinase activity was the only significant predictive marker for response to platinum-based therapy, with higher response rates seen in patients with higher levels of activity (P = 0.045). Cyclin E protein levels did not predict for platinum sensitivity (P = 0.20). In contrast, cyclin E protein levels, but not cyclin E - associated kinase activity, was a significant predictor for freedom from recurrence (P = 0.01 and P = 0.25, respectively). Conclusions: Cyclin E overexpression and cyclin E - associated kinase activity have distinct roles in predicting for response to chemotherapy and outcome in ovarian cancer patients. These results suggest a compartmentalization of cyclin E functions in the oncogenic process.
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U2 - 10.1158/1078-0432.CCR-07-0142
DO - 10.1158/1078-0432.CCR-07-0142
M3 - Article
C2 - 17699858
AN - SCOPUS:34548080298
SN - 1078-0432
VL - 13
SP - 4800
EP - 4806
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -