Gene silencing of A-kinase anchor protein 4 inhibits cervical cancer growth in vitro and in vivo. Cancer Gene Ther 2013 Jul;20(7):413-20
Date
06/15/2013Pubmed ID
23764900DOI
10.1038/cgt.2013.32Scopus ID
2-s2.0-84880924008 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Earlier, we reported an association of A-kinase anchor protein 4 (AKAP4) expression in cervical cancer patient specimens, indicating its implications as an immunotherapeutic target. In this study, we investigated the possible role of AKAP4 in cervical carcinogenesis. AKAP4 messenger RNA and protein expression was assessed in four cervical cancer cell line models, C-33A, CaSki, HeLa and SiHa. Gene silencing approach was employed to investigate the potential role of AKAP4 in cellular growth, proliferation, colony-forming ability, migration and invasion in aggressive squamous cell carcinoma cells (SiHa). Further, the effect of downregulation of AKAP4 on tumor growth was examined in the cervical cancer xenograft model in nude mice. Our data clearly indicated that AKAP4 was expressed in all cervical cancer cells at the gene and protein level. We also observed distinct cytoplasmic and surface localization by indirect immunofluorescence and flow cytometry, respectively. Ablation of AKAP4 protein caused significant inhibition in cellular proliferation, colony-forming ability, migration and invasion ability of SiHa cells. Further, gene silencing of AKAP4 also resulted in reduced tumor growth in nude mice in vivo. Collectively, AKAP4 surface localization and its significant association with malignant properties of cervical cancer cells imply its clinical utility as an immunotherapeutic target.
Author List
Saini S, Agarwal S, Sinha A, Verma A, Parashar D, Gupta N, Ansari AS, Lohiya NK, Jagadish N, Suri AAuthor
Deepak Parashar PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
A Kinase Anchor ProteinsAnimals
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Gene Expression
Gene Knockdown Techniques
Humans
Mice, Nude
Neoplasm Transplantation
Protein Transport
RNA Interference
RNA, Small Interfering
Tumor Burden
Uterine Cervical Neoplasms
