Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer.

Abstract

BACKGROUND:

The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells. Here, we investigated API5 expression in cervical cancer, its clinical significance, and its relationship with phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in development and progression of cervical cancer.

METHODS:

API5 effects on cell growth were assessed in cervical cancer cell lines. API5 and pERK1/2 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 173 primary cervical cancers, 306 cervical intraepithelial neoplasias (CINs), and 429 matched normal tissues.

RESULTS:

API5 overexpression promoted cell proliferation and colony formation in CaSki cells, whereas API5 knockdown inhibited the both properties in HeLa cells. Immunohistochemical staining showed that API5 expression increased during the normal to tumor transition of cervical carcinoma (P < 0.001), and this increased expression was significantly associated with tumor stage (P = 0.004), tumor grade (P < 0.001), and chemo-radiation response (P = 0.004). API5 expression levels were positively associated with pERK1/2 in cervical cancer (P < 0.001) and high grade CIN (P = 0.031). In multivariate analysis, API5+ (P = 0.039) and combined API5+/pERK1/2+ (P = 0.032) were independent prognostic factors for overall survival.

CONCLUSIONS:

API5 expression is associated with pERK1/2 in a subset of cervical cancer patients and its expression predicts poor overall survival, supporting that API5 may be a promising novel target for therapeutic interventions.

• Authors: Hanbyoul Cho, Joon-Yong Chung, Kwon-Ho Song, Kyung Hee Noh, Bo Wook Kim, Eun Joo Chung, Kris Ylaya, Jin Hee Kim, Tae Woo Kim, Stephen M Hewitt, Jae-Hoon Kim
• Journal: BMC cancer (BMC Cancer) Vol. 14 Pg. 545 (Jul 28 2014) ISSN: 1471-2407 [Electronic] England
• PMID: 25070070 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• API5 protein, human
• Apoptosis Regulatory Proteins
• Nuclear Proteins
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Apoptosis Regulatory Proteins (metabolism)
• Cell Line, Tumor
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• HeLa Cells
• Humans
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Nuclear Proteins (metabolism)
• Phosphorylation
• Prognosis
• Survival Analysis
• Tissue Array Analysis
• Uterine Cervical Neoplasms (metabolism, pathology)