Blockade Of Growth Hormone Receptor Inhibits HER2 Overexpressing Breast Cancer Cell Proliferation

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 292-325-Breast & Prostate Cancer
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-301
Arunkumar Arumugam*1, Thiyagarajan Boopalan2, Sushmita B Nandy1, Rebecca Lopez3, Christina Gutierrez4 and Rajkumar Lakshmanaswamy5
1Texas Tech University Health Sci, El Paso, TX, 2Texas Tech Univ, El Paso, TX, 3Texas Tech University Health Sciences, El Paso, TX, 4Texas Tech University Health Sciences Center, El Paso, 5Texas Tech Univ Health Sci Ctr, El Paso, TX
About 25%–30% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2). Trastuzumab, a recombinant humanized monoclonal antibody targeted to the extracellular domain of the HER2 is currently used along with other chemotherapeutic agents to treat HER2 overexpressing breast cancer. Resistance to trastuzumab often develops during the course of treatment and the chemotherapeutic drugs are not effective in resistant tumors. Combination therapies are currently employed for the inhibition of trastuzumab resistant breast cancer cells. Growth Hormone (GH) plays a vital role in breast cancer (BC) development and chemoresistance against doxorubicin. Induced expression of GHR associated with aggressive growth of cancer cells. In the present investigation we demonstrate that by blocking GH receptor along with trastuzumab, inhibited HER2 overexpressing breast cancer cell proliferation. GHR was knockeddown in the HER2 overexpressing breast cancer cell lines (SKBr3 and BT20) and examined for cell proliferation and induction of apoptosis. The downstream signaling of GHR and HER2 was also analyzed after treatment with HER2 inhibitor trastuzumab and GHR blocker pegvisomant. The results showed that knockdown of GHR alone causes 40% reduction in cell proliferation. Moreover, the induction of apoptosis was elevated in the GHR knockdown cells.  Activation of JAK/STAT pathway was inhibited along with reduced phosphorylation of HER2. The combination of trastuzumab and pegvisomant treatment showed significant reduction in the proliferation and increased apoptotic cell death. Overall, the results suggest that by blocking GHR along with HER2 could be a useful treatment strategy against HER2 overexpressing breast cancers.

Nothing to Disclose: AA, TB, SBN, RL, CG, RL

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