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 language | English |
|---|---|
| Pages (from-to) | 389-397 |
| Number of pages | 9 |
| Journal | International Journal of Molecular Medicine |
| Volume | 22 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Sep 2008 |
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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 journal › Article
}
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 -