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Clinical Significance, Functional Role And Molecular Mechanism Of 2’-O-Methyltransferase Ftsj3 In Promoting Cancer Progression, Morenci Manning-Powell

Wayne State University Dissertations

2’-O-methylation (2’-O-Me), one of the most common modifications within RNA, has multiple roles in modulating RNA structure, stability, and interactions, as well as gene transcription and translation. We previously performed integrative genomic and transcriptomic analysis of 58 RNA methyltransferases, and identified FTSJ3 (FtsJ RNA 2ʹ-O-methyltransferase 3) as significantly amplified/overexpressed in breast cancer. Knockdown of FTSJ3 inhibits breast cancer cell growth in vitro. However, the clinical significance, functional role, and molecular mechanism of FTSJ3 in human cancer remains to be elucidated. In the present study, we first analyzed the differential mRNA and protein expression of FTSJ3 between tumor and normal tissues …

The Role Of Bca2 In Regulation Of Warburg-Like Glucose And Lactate Metabolism In Breast Cancer Cell Lines, Richard T. Arkwright Iii

Wayne State University Dissertations

Modified metabolism is a hallmark of cancer cell biology known as “The Warburg Effect,” characterized by increased glucose-consumption and lactate-production, providing the metabolites and energy necessary for rapid proliferation. Breast-cancer-associated-gene-2 (BCA2) is an E3-Ub-ligase known to modulate AMPK, the “master-regulator of energy-homeostasis.” BCA2 is an oncogene associated with poor patient-survival and breast cancer invasiveness. Phospho-proteomic analysis of siBCA2-MDA-MB-231 knockdown-(KD) revealed enrichment of Nicotinamide-Nucleotide-Adenylyl-transferase-1 (NMNAT1), an essential enzyme in nuclear NAD-synthesis and a tumor-suppressor.

Initial experiments demonstrated that glucose concentration was positively correlated with BCA2 and inversely with NMNAT1 protein expression. shBCA2-KD in MDA-MB-468/-231 reproduced the inverse correlation between BCA2 and …

Expression And Regulation Of Map Kinase Phosphatases 1 And 2 In Breast Cancer Tamoxifen Sensitivity, Kelly Haagenson

Wayne State University Dissertations

ABSTRACT

EXPRESSION AND REGULATION OF MAP KINASE PHOSPHATASES 1 and 2 IN BREAST CANCER TAMOXIFEN SENSITIVITY

by

KELLY K. HAAGENSON

May 2013

Advisor: Dr. Malathy Shekhar

Co-Advisor: Dr. Gen Sheng Wu

Major: Cancer Biology

Degree: Doctor of Philosophy

The deregulation of cell signaling is a very important component in the development and progression of cancer. One group of signaling molecules that has been implicated in these processes is the Mitogen-Activated Protein Kinase (MAPK) family which consists of three major branches in mammalian cells: ERK, JNK and p38. The activity of these kinases has wide-ranging effects within the cell and must …

The Bca2 And Ampk Paradigm: Unraveling The Cancer Connection, Daniela (Buac) Ventro

Wayne State University Dissertations

THE BCA2 & AMPK PARADIGM: UNRAVELING THE CANCER CONNECTION

By

DANIELA (BUAC) VENTRO

December 2013

Advisor: Dr. Q Ping Dou and Angelika M. Burger (deceased)

Major: Cancer Biology

Degree: Doctor of Philosophy

Adenosine monophosphate-activated kinase (AMPK), a master regulator of cellular energy homeostasis, has emerged as a promising molecular target in the prevention of breast cancer, and phase II and III clinical trials using the FDA-approved, AMPK activating, anti-diabetic drug metformin are promising in this regard, but the question of why metformin is protective for some women but not others still remains. Breast Cancer Associated Gene 2 (BCA2/Rabring7/RNF115), a novel …

The Lived Experience Of African American Women With Breast Cancer-Related Lymphedema, Deborah Collins-Bohler

Wayne State University Dissertations

African American patients have been reported as having a greater number of aggressive cancer treatments compared to Caucasians (McWayne & Heiney, 2005; Meeske et al., 2009; Ridner & Dietrich, 2008), and have higher incidence of BCRLE due axillary lymph node dissection (ALND) and radiation intervention (Thomas-MacLean, Miedema, Tateemichi, 2005). Research regarding BCRLE has used BCRLE samples comprised almost exclusively of married and well-educated Caucasian women. Few studies (Bowman, Deimling, Smerglia, Sage, & Kahana, 2003; Eversley et al., 2005; Joslyn, 2002; McWayne & Heiney, 2005) have included sizeable numbers of African American breast cancer survivors. No studies have been found that …