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Full-Text Articles in Life Sciences
The P53 Independent Functions Of Estrogen-Activated Mdm2 In Cell Signaling And Mammary Architecture, Nandini Kundu
The P53 Independent Functions Of Estrogen-Activated Mdm2 In Cell Signaling And Mammary Architecture, Nandini Kundu
Dissertations, Theses, and Capstone Projects
Estrogen receptor positive (ER+) breast cancers often have MDM2 overexpression indicating a critical role for MDM2 in breast cancer tumorigenesis. The cancer genome atlas (TCGA) found that increased MDM2 expression is one of the four pathways that correlate with all breast cancer subtypes. MDM2 is mainly known as the negative regulator of wild type p53. However, aggressive breast cancers often have MDM2 overexpression and mutant p53 (mtp53). We previously reported that MDM2 provides an estrogen-mediated proliferative advantage to MCF-7 breast cancer cells (ER+, MDM2 overexpression, wild type p53), independent of wild type p53 in both 2D and 3D culture conditions. …
Estrogen-Activated Mdm2 Disrupts Mammary Tissue Architecture Through A P53-Independent Pathway, Nandini Kundu, Angelika Brekman, Jun Yeob Kim, Gu Xiano, Chong Gao, Jill Bargonetti
Estrogen-Activated Mdm2 Disrupts Mammary Tissue Architecture Through A P53-Independent Pathway, Nandini Kundu, Angelika Brekman, Jun Yeob Kim, Gu Xiano, Chong Gao, Jill Bargonetti
Publications and Research
The Cancer Genome Atlas (TCGA) data indicate that high MDM2 expression correlates with all subtypes of breast cancer. Overexpression of MDM2 drives breast oncogenesis in the presence of wild-type or mutant p53 (mtp53). Importantly, estrogen-receptor positive (ER+) breast cancers overexpress MDM2 and estrogen mediates this expression. We previously demonstrated that this estrogen-MDM2 axis activates the proliferation of breast cancer cell lines T47D (mtp53 L194F) and MCF7 (wild-type p53) in a manner independent of increased degradation of wildtype p53 (ie, p53-independently). Herein we present data supporting the role of the estrogen-MDM2 axis in regulating cell proliferation and mammary tissue architecture of …
Targeting Apoptotic Pathways To Overcome Drug Resistance In Acute Myeloid Leukemia, Rongqing Pan
Targeting Apoptotic Pathways To Overcome Drug Resistance In Acute Myeloid Leukemia, Rongqing Pan
Dissertations & Theses (Open Access)
Evasion of apoptosis is integral to tumorigenesis and drug resistance. BCL-2 and p53 proteins represent two focal nodes in convergent apoptosis signaling. Upregulation of anti-apoptotic BCL-2 family members and inactivation of p53 functions are two canonical approaches exploited by cancer cells to escape apoptosis. In the current study, we find that BCL-2 protein is highly expressed in acute myeloid leukemia (AML) cells. BCL-2–specific inhibitor ABT-199 potently induces mitochondrial apoptosis in AML cells and effectively kills AML stem/progenitor cells. Our biomarker studies demonstrate that both BH3 profiling and the expression profiling of BCL-2 proteins may serve as predictive biomarkers for the …