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Co-Overexpression of GEP100 and AMAP1 Proteins Correlates with Rapid Local Recurrence after Breast Conservative Therapy

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Title: Co-Overexpression of GEP100 and AMAP1 Proteins Correlates with Rapid Local Recurrence after Breast Conservative Therapy
Authors: Kinoshita, Rumiko Browse this author
Nam, Jin-Min Browse this author
Ito, Yoichi M. Browse this author
Hatanaka, Kanako C. Browse this author
Hashimoto, Ari Browse this author →KAKEN DB
Handa, Haruka Browse this author
Otsuka, Yutaro Browse this author
Hashimoto, Shigeru Browse this author →KAKEN DB
Onodera, Yasuhito Browse this author →KAKEN DB
Hosoda, Mitsuchika Browse this author →KAKEN DB
Onodera, Shunsuke Browse this author
Shimizu, Shinichi Browse this author →KAKEN DB
Tanaka, Shinya Browse this author →KAKEN DB
Shirato, Hiroki Browse this author →KAKEN DB
Tanino, Mishie Browse this author →KAKEN DB
Sabe, Hisataka Browse this author →KAKEN DB
Issue Date: 7-Oct-2013
Publisher: Public library science
Journal Title: Plos one
Volume: 8
Issue: 10
Start Page: e76791
Publisher DOI: 10.1371/journal.pone.0076791
Abstract: A major problem of current cancer research and therapy is prediction of tumor recurrence after initial treatment, rather than the simple biological characterization of the malignancy and proliferative properties of tumors. Breast conservation therapy (BCT) is a well-approved, standard treatment for patients with early stages of breast cancer, which consists of lumpectomy and whole-breast irradiation. In spite of extensive studies, only 'age' and 'Ki-67 positivity' have been identified to be well correlated with local recurrence after BCT. An Arf6 pathway, activated by GEP100 under receptor tyrosine kinases (RTKs) and employs AMAP1 as its effector, is crucial for invasion and metastasis of some breast cancer cells. This pathway activates beta 1 integrins and perturbs E-cadherin-based adhesions, hence appears to be integral for epithelial-mesenchymal transdifferentiation (EMT). We here show that expression of the Arf6 pathway components statistically correlates with rapid local recurrence after BCT. We retrospectively analyzed four hundred seventy-nine patients who received BCT in Hokkaido University Hospital, and found 20 patients had local recurrence. We then analyzed pathological samples of patients who experienced local recurrence by use of Kaplan-Meier analysis, Stepwise regression analysis and the t-test, coupled with immunostaining, and found that co-overexpression of GEP100 and AMAP1 correlates with rapidity of the local recurrence. Their margin-status, node-positivity, and estrogen receptor (ER)-or progesterone receptor (PgR)positivity did not correlated with the rapidity. This study is the first to show that expression of a certain set of proteins correlates with the rapidity of local recurrence. Our results are useful not only for prediction, but highlight the possibility of developing novel strategies to block local recurrence. We also discuss why mRNAs encoding these proteins have not been identified to correlate with local recurrence by previous conventional gene expression profiling analyses.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 谷野 美智枝

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