Characterization of plant homeodomain finger protein 11 (PHF11), a candidate tumor suppressor, in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a common cancer worldwide with a high mortality rate. High occurrence of ESCC is observed in Southeast Asia. Identification and characterization of ESCC important tumor suppressor genes will be highly beneficial to the understanding of the disease and for the early diagnosis and improvement of therapy for the cancer. In our previous microcell-mediated chromosome transfer (MMCT) studies, the transfer of an intact chromosome 13 into the recipient ESCC cell line revealed the tumor suppressive ability and putative tumor suppressive function of chromosome 13 in ESCC. One candidate gene, Plant-Homeodomain Finger Protein 11(PHF11), was identified from the study and selected for further functional studies in this current study. PHF11, located on chromosomal region 13q14, contains two plant homeodomain fingers and is a member of the PHD finger protein family. PHF11was reported to be associated with asthma and atopic diseases, yet no studies of PHF11havebeen reported in cancer to date. This study is the first to report the functional role of PHF11in tumor suppression. In this current study, two isoforms of PHF11, PHF11aand b, were reintroduced into ESCC cell lines by methods of transient tranfection and lentiviral-infection. In vitro studies showed both isoforms have cell proliferation and colony-formation inhibition abilities. In the nude mouse tumorigenicity assay, however, it was revealed that only thePHF11aisoform was tumor suppressive in vivo. No differences in angiogenesis-related factors and apoptosis-related factors were observed in PHF11a-and b-expressing cells. Further studies by Western blotting analysis and flow cytometry analysis showed that PHF11amay play a role in delaying cell cycle progression by the down-regulation of cyclin expression, while the PHF11bmay be functionally inactive, The results of this current study further confirm the tumor suppressive role of PHF11ain ESCC, whereas the PHF11b isoform was unable to suppress tumor formation in vivo. Further study of the PHF11 isoforms to identify their differential functions and interacting partners will provide a better understanding of the mechanism by which PHF11a suppressestumor growth.published_or_final_versionClinical OncologyMasterMaster of Philosoph