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.
Bibliographical noteFunding Information:
This work was supported in part by grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013M3A9D3045881, 2011–0005230, 2011–0010286, and 2011–0007146), faculty research grants from Yonsei University College of Medicine for 2014 (6-2014-0072), and Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
TMAs were constructed from 479 formalin-fixed, paraffin-embedded tissue specimens, including 429 nonadjacent normal epithelial tissues. Some of the paraffin blocks were provided by the Korea Gynecologic Cancer Bank through Bio & Medical Technology Development Program of the Ministry of Education, Science and Technology, Korea. Briefly, hematoxylin and eosin (H&E) stained full-face sections of all cases were reviewed by an institutional pathologist to define representative tumor areas. Four 1.0 mm diameter tissue cores, consisting of matched tumor specimen and normal epithelial tissues, were retrieved from formalin-fixed, paraffin-embedded tissue blocks and arrayed on a 38 × 25 mm recipient paraffin block using a manual tissue arrayer MTA-1 (Beecher Instruments Inc., Silver Spring, MD). Sections were cut at 5 μm with a microtome and placed on charged glass slides. The presence of tumor tissues on the sections was verified by H&E staining.
© 2014 Cho et al.; licensee BioMed Central Ltd.
All Science Journal Classification (ASJC) codes
- Cancer Research