Screening for transcription factors and their regulatory small molecules involved in regulating the functions of CL1-5 cancer cells under the effects of macrophage-conditioned medium.

Abstract

Many reports have inferred that macrophages can interact with tumor cells in the tumor microenvironment (TME) in a vicious cycle of tumor development; however, the changes in gene expression in tumor cells under the effects of macrophages are still largely unknown. The present study was carried out to illustrate the changes in the gene expression profile in lung cancer cells under the effects of macrophage-conditioned medium. Gene expression profile data were derived from the GEO database GSE9315. The GSM234968 sample was derived from a highly invasive human pulmonary adenocarcinoma cell line, CL1-5, and was treated with conditioned medium (supernatant of a culture solution of human monocyte THP-1). The GSM234967 sample that was not treated with the conditioned medium was used as a control. GO and KEGG enrichment analyses were carried out using DAVID software, and visualization networks were constructed using Cytoscape software. The results showed that 40 differentially expressed genes were annotated. Five differentially expressed transcription factors were identified, EIF2B4, EIF2B5, JUNB, GNG11 and HMGB2, which were all related to 'stress' and 'responses'. The gene cluster of JUNB was mainly enriched in cancer-related pathways, 'Wnt signaling pathway' and 'MAPK signaling pathway'. Finally, 10 small molecules, thioridazine, resveratrol, astemizole, ciclopirox, calmidazolium, etoposide, anisomycin, pyrvinium, azacyclonol and terfenadine, which may act on transcription factors, were identified using the CMap database. In conclusion, we identified transcription factors playing key roles in tumor cells under the effects of macrophages in order to provide new clues for blocking this vicious cycle of tumor development.

• Authors: Dongbo Xue, Ming Lu, Bo Gao, Xin Qiao, Yingmei Zhang
• Journal: Oncology reports (Oncol Rep) Vol. 31 Issue 3 Pg. 1323-33 (Mar 2014) ISSN: 1791-2431 [Electronic] Greece
• PMID: 24366584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Culture Media, Conditioned
• JunB protein, human
• Transcription Factors

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Culture Media, Conditioned
• Drug Screening Assays, Antitumor
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Regulatory Networks
• Humans
• Macrophages (metabolism)
• Molecular Sequence Annotation
• Multigene Family
• Oligonucleotide Array Sequence Analysis
• Transcription Factors (genetics, metabolism)
• Transcriptome (drug effects)
• Tumor Microenvironment