Abstract Form
International Symposium on Translational Cancer Research
in conjunction with the15
thAnnual Meeting of the Taiwan Cooperative Oncology Group
Nov. 20-21, 2011 Academia Sinica, Taipei, Taiwan
Abstract. No. ＿＿ (for Secretariat use only) Please TYPE all information.
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Speaker ● Attendee [ ＿＿ Abroad, ＿●＿ Local; Online Registration No. 251 ] Abstract Fields□
Clinical Cancer Research ● Basic Cancer ResearchAuthor Name (English) Meng-Chieh Yu (Chinese) 游孟潔
Institution Center for Molecular Medicine, China Medical University and Hospital, Taichung 404, Taiwan,
Department Graduate Institute of Cancer Biology, and the Ph.D. program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404, Taiwan
TEL 04-22052121 FAX 04-22333496 E-Mail [email protected]
Kinase-inactive EGFR stabilizes COX-2 mRNA to mediate lapatinib-promoted aggressiveness of triple-negative breast cancer cells
Meng-Chieh Yu, Te-Chun Hsia, Chih-Yen Tu , Ya-Ling Wei , Sheng-Chieh Hsu, Shing-Ling Tsai, Yi-Shian Yang , Min-Hsiang Hsu , Chia-Jui Yen , Chih-Yang Huang , Yun-Ju Chen , Mien-Chie Hung, Wei-Chien Huang
Graduate Institute of Cancer Biology, and the Ph.D. program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404, Taiwan,
Center for Molecular Medicine, China Medical University and Hospital, Taichung 404, Taiwan,
Background
Addition of lapatinib, a dual EGFR/HER2 kinase inhibitor, to chemotherapy benefits patients with advanced HER2-positive breast cancers, but has been shown to worsen the overall survival of breast cancer patients with triple-negative tumors. However, it is unknown whether lapatinib elicits any negative effects on these HER2-negative cancer cells. The aim of this study was to investigate the effects of lapatinib on cell proliferation, motility, and the underlying mechanisms in triple-negative breast cancer cells.
Methods
Triple-negative breast cancer cell lines were chronically treated with lapatinib to establish the lapatinib-selected clones. The viability and metastasis of these lapatinib-selected cells in vitro and in vivo were examined by using MTT, wound healing, and transwell assays as well as orthotopic xenograft mice model. Luciferase reporter gene, immunoblot, and RNA-immunoprecipitation assays were used to investigate the molecular mechanisms of action.
Results
Our results showed that treatment with lapatinib alone promoted aggressiveness of triple-negative cells without affecting their viability, leading to axillary metastases and a worse survival in orthotopic xenograft mice. The lapatinib-increased cell motility was caused by elevation of EGFR through down-regulation of microRNA-7 and by subsequent overexpression of cyclooxygenase-2 (COX-2). Strikingly, the elevated EGFR, independent of its kinase activity, stabilized COX-2 expression through enhancing HuR binding to COX-2 mRNA.
Conclusions
Our results suggest that lapatinib may aggravate triple-negative tumors through up-regulation of EGFR and COX-2, providing a potential explanation for the worse clinical outcome of triple-negative patients who receiving lapatinib-based treatment.
Abstract Submission
All abstracts are strongly encouraged to be submitted through the online abstract submission system (http://istcr.nhri.org.tw/istcr2011/apply_abstract.asp), and the authors must register online in advance.
The abstract submission ends up on Sept. 30, 2011.
Abstract Themes
Abstract related to the basic and clinical research of cancer are cordially welcomed.
Notification of Acceptance
Abstracts will be reviewed by the Scientific Committee. Successful submissions will be notified with detailed information no later than October 31, 2011.
The Scientific Committee will offer Poster Sessions to accepted abstracts.
The accepted abstracts will be published as a supplement to the symposium information.
Please note that if you are successful in your abstract submission, it is required that you pay for your own travel costs to and during the symposium.
Abstract Format
The abstract should be written in English in Microsoft Word format, typed in Times New Roman font, size 12, single space.
The abstract should comprise "Title", "Author", "Affiliation" and "Abstract Text" four elements.
The "Abstract Text" should cover "Background", "Methods", "Results" and "Conclusions" four sections and is limited to 250 words.
The "Abstract Title" should be in bold and initial capital.
Authors' names should be in initial capital and begin with full first name, middle initial and last name. The presenting author should be indicated by underline.
Authors' institutional affiliations should be indicated with superscript Arabic numbers. For each affiliation, type the name of the institution, city, state and country.
Poster Award
The Poster Award will be given to distinguished posters presented at ISTCR 2011. The Scientific Committee will make the final judgment for the awards. All prizes will be awarded in the Closing Remarks on Nov. 21, 2011.
To appreciate participation and presentation, the Organizing Committee will provide financial incentives and a certificate for outstanding posters.
