Abstract
BackgroundThe 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.MethodsAPI5 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.ResultsAPI5 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.ConclusionsAPI5 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-545) contains supplementary material, which is available to authorized users.
Highlights
The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells
We further analyzed the expression of API5 protein in cytoplasmic and nuclear fractions of the HeLa cells which have the highest expression of API5 among the cervical cancer cell lines examined by western blot analysis
We observed a similar localization pattern of endogenous API5 in CaSki cells after immunofluorescence staining (Additional file 1: Figure S1). These results demonstrate that API5 expresses in cervical cancer cell lines and is primarily localized in nucleus
Summary
The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells. 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. Optimal treatment of early-stage cervical cancer is either radical surgery or radiotherapy. Acquired resistance to apoptosis is a well-known hallmark of cancer and contributes to tumorigenesis and the malignant phenotype [7]. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are members of mitogen activated protein kinase (MAPKs), mediates cell proliferation. The activation of ERK1/2 induces metaplasia and development of tumors via cell cycle arrest and apoptosis inhibition [8,9]
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