TY - JOUR
T1 - Roscovitine confers tumor suppressive effect on therapy-resistant breast tumor cells
AU - Nair, Binoj C.
AU - Vallabhaneni, Sreeram
AU - Tekmal, Rajeshwar R.
AU - Vadlamudi, Ratna K.
N1 - Funding Information:
This study is supported by NIH grant CA0095681 (R.K. Vadlamudi) and Department of Defense pre-doctoral grant W81XWH-09-1-0010 (B.C. Nair).
PY - 2011/6/11
Y1 - 2011/6/11
N2 - Introduction: Current clinical strategies for treating hormonal breast cancer involve the use of anti-estrogens that block estrogen receptor (ER)α functions and aromatase inhibitors that decrease local and systemic estrogen production. Both of these strategies improve outcomes for ERα-positive breast cancer patients, however, development of therapy resistance remains a major clinical problem. Divergent molecular pathways have been described for this resistant phenotype and interestingly, the majority of downstream events in these resistance pathways converge upon the modulation of cell cycle regulatory proteins including aberrant activation of cyclin dependent kinase 2 (CDK2). In this study, we examined whether the CDK inhibitor roscovitine confers a tumor suppressive effect on therapy-resistant breast epithelial cells.Methods: Using various in vitro and in vivo assays, we tested the effect of roscovitine on three hormonal therapy-resistant model cells: (a) MCF-7-TamR (acquired tamoxifen resistance model); (b) MCF-7-LTLTca (acquired letrozole resistance model); and
AB - Introduction: Current clinical strategies for treating hormonal breast cancer involve the use of anti-estrogens that block estrogen receptor (ER)α functions and aromatase inhibitors that decrease local and systemic estrogen production. Both of these strategies improve outcomes for ERα-positive breast cancer patients, however, development of therapy resistance remains a major clinical problem. Divergent molecular pathways have been described for this resistant phenotype and interestingly, the majority of downstream events in these resistance pathways converge upon the modulation of cell cycle regulatory proteins including aberrant activation of cyclin dependent kinase 2 (CDK2). In this study, we examined whether the CDK inhibitor roscovitine confers a tumor suppressive effect on therapy-resistant breast epithelial cells.Methods: Using various in vitro and in vivo assays, we tested the effect of roscovitine on three hormonal therapy-resistant model cells: (a) MCF-7-TamR (acquired tamoxifen resistance model); (b) MCF-7-LTLTca (acquired letrozole resistance model); and
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U2 - 10.1186/bcr2929
DO - 10.1186/bcr2929
M3 - Article
C2 - 21834972
AN - SCOPUS:80053209796
SN - 1465-5411
VL - 13
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 3
M1 - R80
ER -