Hepsin inhibits the cell growth of endometrial cancer

Keiichiro Nakamura, Norio Takamoto, Fernando Abarzua, Atsushi Hongo, Junichi Kodama, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed chymotrypsin-like serine protease and a member of the family of type II transmembrane serine proteases. To date, little is known about its precise mechanisms of action. We investigated the biological functions and effects in vitro and in vivo of Hepsin, using endometrial cancer cell lines transfected with Hepsin. In stably transfected Ishikawa/Hepsin cell lines (Hepsin-10 and -12), we observed a significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro. Furthermore, in a xenograft model, growth inhibitory effects were observed when compared with the effects of mock-transfected cells used as a control. Overall, Hepsin showed potential inhibitory effects mediated by the induction of 14-3-3σ expression which leads to both cell cycle arrest at the G2/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL.

Original languageEnglish
Pages (from-to)389-397
Number of pages9
JournalInternational Journal of Molecular Medicine
Volume22
Issue number3
DOIs
Publication statusPublished - Sep 2008

Fingerprint

Endometrial Neoplasms
Growth
Serine Proteases
Chymases
Cyclin B
Cyclin A
Cell Line
G2 Phase
Cell Cycle Checkpoints
Heterografts
Cell Division
Agar
hepsin
Radiotherapy
Recurrence
Drug Therapy
Therapeutics

Keywords

  • Cell cycle
  • Endometrial cancer
  • Hepsin

ASJC Scopus subject areas

  • Genetics

Cite this

Hepsin inhibits the cell growth of endometrial cancer. / Nakamura, Keiichiro; Takamoto, Norio; Abarzua, Fernando; Hongo, Atsushi; Kodama, Junichi; Nasu, Yasutomo; Kumon, Hiromi; Hiramatsu, Yuji.

In: International Journal of Molecular Medicine, Vol. 22, No. 3, 09.2008, p. 389-397.

Research output: Contribution to journalArticle

Nakamura, K, Takamoto, N, Abarzua, F, Hongo, A, Kodama, J, Nasu, Y, Kumon, H & Hiramatsu, Y 2008, 'Hepsin inhibits the cell growth of endometrial cancer', International Journal of Molecular Medicine, vol. 22, no. 3, pp. 389-397. https://doi.org/10.3892/ijmm_00000035
Nakamura, Keiichiro ; Takamoto, Norio ; Abarzua, Fernando ; Hongo, Atsushi ; Kodama, Junichi ; Nasu, Yasutomo ; Kumon, Hiromi ; Hiramatsu, Yuji. / Hepsin inhibits the cell growth of endometrial cancer. In: International Journal of Molecular Medicine. 2008 ; Vol. 22, No. 3. pp. 389-397.
@article{a013cd8d3f4f45638b9506a01ade5310,
title = "Hepsin inhibits the cell growth of endometrial cancer",
abstract = "Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed chymotrypsin-like serine protease and a member of the family of type II transmembrane serine proteases. To date, little is known about its precise mechanisms of action. We investigated the biological functions and effects in vitro and in vivo of Hepsin, using endometrial cancer cell lines transfected with Hepsin. In stably transfected Ishikawa/Hepsin cell lines (Hepsin-10 and -12), we observed a significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro. Furthermore, in a xenograft model, growth inhibitory effects were observed when compared with the effects of mock-transfected cells used as a control. Overall, Hepsin showed potential inhibitory effects mediated by the induction of 14-3-3σ expression which leads to both cell cycle arrest at the G2/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL.",
keywords = "Cell cycle, Endometrial cancer, Hepsin",
author = "Keiichiro Nakamura and Norio Takamoto and Fernando Abarzua and Atsushi Hongo and Junichi Kodama and Yasutomo Nasu and Hiromi Kumon and Yuji Hiramatsu",
year = "2008",
month = "9",
doi = "10.3892/ijmm_00000035",
language = "English",
volume = "22",
pages = "389--397",
journal = "International Journal of Molecular Medicine",
issn = "1107-3756",
publisher = "Spandidos Publications",
number = "3",

}

TY - JOUR

T1 - Hepsin inhibits the cell growth of endometrial cancer

AU - Nakamura, Keiichiro

AU - Takamoto, Norio

AU - Abarzua, Fernando

AU - Hongo, Atsushi

AU - Kodama, Junichi

AU - Nasu, Yasutomo

AU - Kumon, Hiromi

AU - Hiramatsu, Yuji

PY - 2008/9

Y1 - 2008/9

N2 - Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed chymotrypsin-like serine protease and a member of the family of type II transmembrane serine proteases. To date, little is known about its precise mechanisms of action. We investigated the biological functions and effects in vitro and in vivo of Hepsin, using endometrial cancer cell lines transfected with Hepsin. In stably transfected Ishikawa/Hepsin cell lines (Hepsin-10 and -12), we observed a significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro. Furthermore, in a xenograft model, growth inhibitory effects were observed when compared with the effects of mock-transfected cells used as a control. Overall, Hepsin showed potential inhibitory effects mediated by the induction of 14-3-3σ expression which leads to both cell cycle arrest at the G2/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL.

AB - Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed chymotrypsin-like serine protease and a member of the family of type II transmembrane serine proteases. To date, little is known about its precise mechanisms of action. We investigated the biological functions and effects in vitro and in vivo of Hepsin, using endometrial cancer cell lines transfected with Hepsin. In stably transfected Ishikawa/Hepsin cell lines (Hepsin-10 and -12), we observed a significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro. Furthermore, in a xenograft model, growth inhibitory effects were observed when compared with the effects of mock-transfected cells used as a control. Overall, Hepsin showed potential inhibitory effects mediated by the induction of 14-3-3σ expression which leads to both cell cycle arrest at the G2/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL.

KW - Cell cycle

KW - Endometrial cancer

KW - Hepsin

UR - http://www.scopus.com/inward/record.url?scp=53049093615&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53049093615&partnerID=8YFLogxK

U2 - 10.3892/ijmm_00000035

DO - 10.3892/ijmm_00000035

M3 - Article

C2 - 18698500

AN - SCOPUS:53049093615

VL - 22

SP - 389

EP - 397

JO - International Journal of Molecular Medicine

JF - International Journal of Molecular Medicine

SN - 1107-3756

IS - 3

ER -