Hepatocyte growth factor activator inhibitor-2 (HAI-2) is a favorable prognosis marker and inhibits cell growth through the apoptotic pathway in cervical cancer

Keiichiro Nakamura, F. Abarzua, A. Hongo, J. Kodama, Yasutomo Nasu, H. Kumon, Y. Hiramatsu

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: In light of the poor prognosis for cervical cancer, research continues into the development of innovative and efficacious treatment modalities for this disease. We investigated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) and evaluated its clinical importance in cervical cancer. Patients and methods: HAI-2 expression was examined in cervical cancer specimens (n = 52) by immunohistochemistry. We further attempted to investigate the biological functions and inhibitory effects of HAI-2 using human papillomavirus (HPV) 16 type SiHa and HPV 18 type HeLa cervical cancer cell lines. Results: There were significant correlations between HAI-2 expression and stage (P = 0.017), lymph node metastasis (P = 0.005) and ovarian metastasis (P = 0.038). Low HAI-2 expression was a significant predictor for a poor prognosis compared with high HAI-2 expression (disease-free survival rate, P = 0.016; overall survival rate, P = 0.021). After transient transfection into the SiHa and HeLa cell lines, HAI-2 showed potential inhibitory effects mediated by reductions in hepsin and matriptase expression, which led to apoptosis by increasing the level of Bak and reducing the level of Bcl-2. Conclusions: The present findings indicate that low HAI-2 expression in cervical cancer may be associated with a poor prognosis. We propose that HAI-2 may represent a therapeutic target for the treatment of cervical cancer.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalAnnals of Oncology
Volume20
Issue number1
DOIs
Publication statusPublished - 2009

Fingerprint

Uterine Cervical Neoplasms
Growth
Survival Rate
Neoplasm Metastasis
Cell Line
Human papillomavirus 18
Human papillomavirus 16
HGF activator
HeLa Cells
Disease-Free Survival
Transfection
Therapeutics
Lymph Nodes
Immunohistochemistry
Apoptosis
Research

Keywords

  • Apoptosis
  • Cervical cancer
  • Favorable prognosis marker, HAI-2

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Hepatocyte growth factor activator inhibitor-2 (HAI-2) is a favorable prognosis marker and inhibits cell growth through the apoptotic pathway in cervical cancer. / Nakamura, Keiichiro; Abarzua, F.; Hongo, A.; Kodama, J.; Nasu, Yasutomo; Kumon, H.; Hiramatsu, Y.

In: Annals of Oncology, Vol. 20, No. 1, 2009, p. 63-70.

Research output: Contribution to journalArticle

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AU - Nasu, Yasutomo

AU - Kumon, H.

AU - Hiramatsu, Y.

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