title: Suppressor of cytokine signaling (SOCS) genes are silenced by DNA hypermethylation and histone deacetylation and regulate response to radiotherapy in cervical cancer cells.
abstract: Suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer.
authors: Department of Obstetrics and Gynecology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea; Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors: Moon-Hong
authors: MH
authors: Kim
authors: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors: Moon-Sun
authors: MS
authors: Kim
authors: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors: Wonwoo
authors: W
authors: Kim
authors: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors: Mi Ae
authors: MA
authors: Kang
authors: Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California, United States of America.
authors: Nicholas A
authors: NA
authors: Cacalano
authors: Department of Obstetrics and Gynecology, Konkuk University Medical Center, Seoul, Korea.
authors: Soon-Beom
authors: SB
authors: Kang
authors: Department of Radiation Oncology, Inje University Sanggye Paik Hospital, Seoul, Korea.
authors: Young-Joo
authors: YJ
authors: Shin
authors: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors: Jae-Hoon
authors: JH
authors: Jeong
mesh_terms: D000107:Acetylation; D015153:Blotting, Western; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy
chemical_list: D016207:Cytokines; D006657:Histones; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors