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

Kinoshita Rumiko; Nam Jin-Min; Ito Yoichi M.; Hatanaka Kanako C.; Hashimoto Ari; Handa Haruka; Otsuka Yutaro; Hashimoto Shigeru; Onodera Yasuhito; Hosoda Mitsuchika; Onodera Shunsuke; Shimizu Shinichi; Tanaka Shinya; Shirato Hiroki; Tanino Mishie; Sabe Hisataka

Title	en Co-Overexpression of GEP100 and AMAP1 Proteins Correlates with Rapid Local Recurrence after Breast Conservative Therapy
Creator	en Kinoshita, Rumiko en Nam, Jin-Min en Ito, Yoichi M. en Hatanaka, Kanako C. en Hashimoto, Ari NRID 1000060390803 en Handa, Haruka en Otsuka, Yutaro en Hashimoto, Shigeru NRID 1000050311303 en Onodera, Yasuhito NRID 1000090435561 en Hosoda, Mitsuchika NRID 1000040443931 en Onodera, Shunsuke en Shimizu, Shinichi NRID 1000050463724 en Tanaka, Shinya NRID 1000070261287 en Shirato, Hiroki NRID 1000020187537 en Tanino, Mishie NRID 1000090360908 en Sabe, Hisataka NRID 1000040187282
Accessrights	open access
Rights	http://creativecommons.org/licenses/by/3.0/ en Creative Commons Attribution 3.0 Unported
Subject	NDC 490
Description	Abstract en 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.
Publisher	en Public library science
Date	Issued2013-10-07
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/53616
Relation	isIdenticalTo DOI https://doi.org/10.1371/journal.pone.0076791
Journal	PISSN 1932-6203 en Plos one Volume Number8 Issue Number10 Page Starte76791
File	fulltext PLoS One_8(10)_e76791.pdf 1.18 MB (application/pdf) Issued2013-10-07
Oaidate	2023-07-26