title: Transcription factor FOXA2-centered transcriptional regulation network in non-small cell lung cancer.
abstract: Lung cancer is the leading cause of cancer-mediated death. Although various therapeutic approaches are used for lung cancer treatment, these mainly target the tumor suppressor p53 transcription factor, which is involved in apoptosis and cell cycle arrest. However, p53-targeted therapies have limited application in lung cancer, since p53 is found to be mutated in more than half of lung cancers. In this study, we propose tumor suppressor FOXA2 as an alternative target protein for therapies against lung cancer and reveal a possible FOXA2-centered transcriptional regulation network by identifying new target genes and binding partners of FOXA2 by using various screening techniques. The genes encoding Glu/Asp-rich carboxy-terminal domain 2 (CITED2), nuclear receptor subfamily 0, group B, member 2 (NR0B2), cell adhesion molecule 1 (CADM1) and BCL2-associated X protein (BAX) were identified as putative target genes of FOXA2. Additionally, the proteins including highly similar to heat shock protein HSP 90-beta (HSP90A), heat shock 70 kDa protein 1A variant (HSPA1A), histone deacetylase 1 (HDAC1) and HDAC3 were identified as novel interacting partners of FOXA2. Moreover, we showed that FOXA2-dependent promoter activation of BAX and p21 genes is significantly reduced via physical interactions between the identified binding partners and FOXA2. These results provide opportunities to understand the FOXA2-centered transcriptional regulation network and novel therapeutic targets to modulate this network in p53-deficient lung cancer.
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Jang
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: An
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Chul-Hong
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea. Electronic address: jungkim@cau.ac.kr.
authors.forename: Jung-Woong
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea. Electronic address: khchoi@cau.ac.kr.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Choi
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks; D051542:Hepatocyte Nuclear Factor 3-beta / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: C496502:FOXA2 protein, human; D051542:Hepatocyte Nuclear Factor 3-beta
keywords: FOXA2; Novel binding proteins; Novel target genes; Transcriptional regulatory network