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  • Undergraduate Poster Abstracts
  • Cancer Biology

    FRI-G12 CELL CULTURE STUDY OF PROTEINS THAT BIND T-DARPP

    • Jonathan Castillo ;
    • Jamil Momand ;

    FRI-G12

    CELL CULTURE STUDY OF PROTEINS THAT BIND T-DARPP

    Jonathan Castillo, Jamil Momand.

    California State University, Los Angeles, Los Angeles, CA.

    Approximately 25% of breast cancers overexpress the human epidermal receptor 2 (HER2/neu), a receptor in the epidermal growth-factor receptor family. Trastuzumab (Herceptin) is a humanized monoclonal antibody which targets the extracellular domain of HER2 growth-factor receptor and is approved to treat patient with HER2-positive metastatic breast cancer. Up to 70% of Her2-positive breast cancers demonstrate a response to Herceptin-based therapies, but resistance almost inevitably arises within a year of the initial response. The protein t-Darpp (tDp) is often overexpressed in resistant breast cancers and confers resistance on naïve cells. Little is known about the mechanism of tDp action. Following the work of others, we seek to determine the binding partners of tDp with the aim to understand the mechanism of the resistance phenotype. A co-immunoprecipitation of HA tagged tDp with 35S-Cys and 35S-Met labeling of SkBr3 cells stably transfected to express tDp.HA was performed. Using an anti-HA and H62 antibody, proteins interacting with tDp were pulled down. Identifying the proteins interacting with tDp will provide insight on its role in the resistance of trastuzumab and could lead to a new target for therapy and/or a biomarker for drug resistance.

    THU-G6 PHYSICAL ACTIVITY IN PREGNANT DAMS REDUCES MAMMARY TUMOR FORMATION IN RAT OFFSPRING

    • Leon Clah ;
    • Ignacio Camarillo ;

    THU-G6

    PHYSICAL ACTIVITY IN PREGNANT DAMS REDUCES MAMMARY TUMOR FORMATION IN RAT OFFSPRING

    Leon Clah, Ignacio Camarillo.

    Purdue University, West Lafayette, IN.

    Breast cancer is the most frequently diagnosed cancer and a leading cause of cancer death among women. Lifestyle factors such as physical activity and diet play a role in attenuating the incidence of breast cancer. Current research is beginning to show that exercise during pregnancy can convey long term health benefits to offspring. Toward this goal, female Sprague Dawley rats were divided into 2 groups, sedentary and exercise, with the exercise group given access to a running wheel during pregnancy. The resulting female pups from sedentary and exercised dams were weaned at 21 days of age and fed a high fat (HF) diet. None of the pups from either of the groups had access to an exercise wheel at any time. At 6-weeks of age, pups were given a single injection of N-Methyl-N-nitrosourea (MNU) intraperitonealy at 50 mg/kg. The study was conducted for 15 weeks and the developing tumors were palpated and measured with calipers. Endpoint analyses revealed that pups from dams that were allowed physical activity (exercise) had a substantially lower tumor incidence (42.86%), as compared to pups from sedentary dams (sedentary), having 100% tumor incidence. Interestingly, exercise pups and the sedentary pups had no histological difference in tumor grading. Collectively, these are the first data to demonstrate that short-term physical activity during pregnancy can lead to reduced tumor development in offspring.

    THU-G7 ROLES FOR EGFR AND IL-6 SIGNALING IN RHABDOMYOSARCOMA PATHOGENESIS

    • Valerie Granados ;
    • Pooja Dalal ;
    • Kathleen Galindo ;
    • Usha Avirneni ;
    • Rene Galindo ;

    THU-G7

    ROLES FOR EGFR AND IL-6 SIGNALING IN RHABDOMYOSARCOMA PATHOGENESIS

    Valerie Granados, Pooja Dalal, Kathleen Galindo, Usha Avirneni, Rene Galindo.

    The University of Texas Southwestern Medical Center, Dallas, TX.

    Rhabdomyosarcoma (RMS) is a skeletal muscle-lineage sarcoma affecting children and adolescents that accounts for approximately 50% of all pediatric sarcoma cases. Clinical treatments for high-risk RMS haven't improved for 3 decades, arguing that new genetic tools and insights are needed to probe and target RMS. Using a signaling network uncovered in a forward genetic screen utilizing an RMS Drosophila model, we focus on evaluating the role of mis-regulated genetic networks in RMS pathobiology. One such pathway uncovered is the epidermal growth factor receptor (EGFR) pathway. In testing FDA-approved drugs that inhibit EGFR (e.g., Tarceva®) in RMS cell lines, we have found that Tarceva reduces RMS cell oncogenicity. Some RMS cell lines tested, however, show minimal to no response to Tarceva, suggesting the hypothesis that alternative/additional pathways facilitate RMS pathogenesis. Several prominent malignancies such as lung and prostate cancer have developed a mechanism to use both EGFR and IL-6 pathways to progress into a malignant phenotype, inducing proliferation, survival, and migration/invasion. We hypothesized that RMS exploits both EGFR and IL-6R pathways to enhance oncogenecity and questioned whether targeting EGFR and IL-6R in tandem would result in an additive/synergistic decrease in RMS pathogenesis. Preliminary results treating RMS cells with an anti-IL-6R monoclonal antibody (mAb) together with Tarceva demonstrates increased blockage of RMS oncogenicity than when treating with Tarceva or IL-6 mAb alone. Since humanized -IL-6R mAb (Tocilizumab®) is approved for clinical treatment of various diseases (e.g., rheumatoid arthritis, ovarian carcinoma), we anticipate Tarceva/IL-6 mAb combination therapy might represent a new avenue to clinically target RMS.

    FRI-G6 DETERMINING IF TRUNCATED DOPAMINE AND CAMP-REGULATED PHOSPHOPROTEIN (T-DARPP) HAS ONCOGENIC POTENTIAL IN BREAST CELLS

    • Aracely Acevedo ;
    • Susan Kane ;
    • Jamil Momand ;

    FRI-G6

    DETERMINING IF TRUNCATED DOPAMINE AND CAMP-REGULATED PHOSPHOPROTEIN (T-DARPP) HAS ONCOGENIC POTENTIAL IN BREAST CELLS

    Aracely Acevedo1, Susan Kane2, Jamil Momand1.

    1California State University, Los Angeles, Los Angeles, CA, 2City of Hope, Duarte, CA.

    Human breast cancers that are found to overexpress Her2 receptor tyrosine kinase are often treated with herceptin (trastuzumab), a humanized monoclonal antibody. Although cancer patients who initially respond to herceptin in combination with chemotherapy have a 5 month increase in median overall survival, the cancer usually builds up resistance. Previous studies have shown Her2+ breast cancer cell lines that acquire resistance to herceptin often overexpress a truncated isoform of Darpp-32 protein, known as t-Darpp. Darpp-32 and t-Darpp are both encoded by the PPP1R1B gene. Darpp-32 (dopamine and cAMP regulated phosphoprotein of 32kD) and t-Darpp modulate the PI3K/Akt signal transduction pathway. In this study, our objective is to determine if t-Darpp is an oncogene. Specifically, the aim is to investigate whether t-Darpp can increase anchorage independent growth of mammalian cells. Additionally, we will determine if endogenous Darpp-32 is necessary for this increased growth. To reach this goal, 4 cell lines will be stably transfected with t-Darpp: MCF10A, MCF-7, NIH3T3, and t-Drp KO MEF. Soft agar colony formation assays (transformation assays) will then be conducted using these mammalian cell lines. We hypothesize that tDarppoverexpression transforms all cell lines and does not require Darpp-32 for its oncogenic transformation. If so, this would confirm the oncogenicity of t-Darpp without the need for endogenous Darpp-32. Determining the oncogenicity of tDarpp will allow us to get a better insight in its role in the PI3K/Akt pathway and how it confers herceptin resistance in Her-2+ breast cancers.