title: TIP30 nuclear translocation negatively regulates EGF-dependent cyclin D1 transcription in human lung adenocarcinoma.
abstract: Aberrant epidermal growth factor (EGF)-dependent signaling plays a key role in the progression of human carcinomas. We found that TIP30, a tumor suppressor protein, translocated into the nucleus of human lung adenocarcinoma cells following EGF treatment, and the selective inhibitors of EGFR signaling pathways blocked this effect. Chromatin immunoprecipitation assays revealed that TIP30 negatively regulated EGF-dependent transcriptional activation of CCND1 through a HDAC1-dependent mechanism. In lung adenocarcinoma patients, the level of nuclear TIP30 was inversely correlated with that of EGFR and cyclin D1. These findings suggest that nuclear TIP30-induced downregulation of cyclin D1 transcription antagonizes EGFR signaling and suppresses tumorigenesis.
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shuai
authors.affiliation: Oncology Department, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yan
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Kang
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China.
authors.forename: Fengsheng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China. Electronic address: luorc0101@163.com.
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China. Electronic address: liaimin2005@163.com.
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C530104:CCND1 protein, human; D014157:Transcription Factors; D019938:Cyclin D1; D004815:Epidermal Growth Factor; D000123:Acetyltransferases; C111246:HTATIP2 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Cyclin D1; EGFR; HDAC1; Lung adenocarcinoma; TIP30