Oncotarget

Research Papers:

Anti-apoptotic Effects of PCP4/PEP19 in Human Breast Cancer Cell Lines: A Novel Oncotarget

Taiji Hamada _, Masakazu Souda, Takuya Yoshimura, Shoko Sasaguri, Kazuhito Hatanaka, Takashi Tasaki, Takako Yoshioka, Yasuyo Ohi, Sohsuke Yamada, Masato Tsutsui, Yoshihisa Umekita and Akihide Tanimoto

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Oncotarget. 2014; 5:6076-6086. https://doi.org/10.18632/oncotarget.2161

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Abstract

Taiji Hamada1, Masakazu Souda1, Takuya Yoshimura2, Shoko Sasaguri1, Kazuhito Hatanaka1, Takashi Tasaki1, Takako Yoshioka1, Yasuyo Ohi3, Sohsuke Yamada4, Masato Tsutsui5, Yoshihisa Umekita6 and Akihide Tanimoto1

1 Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

2 Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

3 Department of Pathology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan.

4 Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

5 Department of Pharmacology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.

6 Division of Organ Pathology, Faculty of Medicine, Tottori University, Yonago, Japan.

Correspondence to:

Akihide Tanimoto, e-mail: [email protected]

Key words: PCP4/PEP19, breast cancer, apoptosis, CaMKK, Akt

Received: April 23, 2014     Accepted: June 23, 2014     Published: July 08, 2014

ABSTRACT

The PCP4/PEP19 is a calmodulin-binding anti-apoptotic peptide in neural cells but its potential role in human cancer has largely been unknown. We investigated the expression of PCP4/PEP19 in human breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 cells, and found that estrogen receptor (ER)-positive MCF-7 and ER-negative SK-BR-3 cells expressed PCP4/PEP19. In the MCF-7 cells, cell proliferation was estrogen-dependent, and PCP4/PEP19 expression was induced by estrogen. In both cell lines, PCP4/PEP19 knockdown induced apoptosis and slightly decreased Akt phosphorylation. Knockdown of calcium/calmodulin-dependent protein kinase kinase 1 (CaMKK1), resulting in decreased phospho-AktThr308, enhanced apoptosis in SK-BR-3 but not in MCF-7 cells. CaMKK2 knockdown moderately decreased phospho-AktThr308 and increased apoptosis in MCF-7 cells but not in SK-BR-3 cells. These data indicated that PCP4/PEP19 regulates apoptosis but exact mechanism is still unknown. PCP4/PEP19 can therefore potentially serve as independent oncotarget for therapy of PCP4/PEP19-positive breast cancers irrespective of ER expression.


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