Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer

• Published in: Oncogene Vol. 27; no. 25; pp. 3635 - 3640
• Main Authors: Kwei, K A, Kim, Y H, Girard, L, Kao, J, Pacyna-Gengelbach, M, Salari, K, Lee, J, Choi, Y-L, Sato, M, Wang, P, Hernandez-Boussard, T, Gazdar, A F, Petersen, I, Minna, J D, Pollack, J R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.06.2008; Nature Publishing; Nature Publishing Group
• Subjects: Apoptosis; Biological and medical sciences; Cell Biology; Cell cycle; Cell growth; Cell Line, Tumor; Cell Lineage; Cell physiology; Cell proliferation; Cell survival; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosome 14; Chromosome Mapping; DNA binding proteins; Fundamental and applied biological sciences. Psychology; Gene amplification; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic aspects; Genome, Human; Genomics; Health aspects; Homeobox; Human Genetics; Humans; Internal Medicine; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical sciences; Medicine; Medicine & Public Health; Models, Biological; Molecular and cellular biology; Neoplasm Metastasis; Nuclear Proteins - biosynthesis; Oligonucleotide Array Sequence Analysis; Oncogenes; Oncology; Physiological aspects; Pneumology; Risk factors; RNA, Small Interfering - metabolism; short-communication; siRNA; Thyroid Nuclear Factor 1; Thyroid transcription factor 1; Transcription factors; Transcription Factors - biosynthesis; Tumor cell lines; Tumorigenesis; Tumors of the respiratory system and mediastinum; United States; lung cancer; TITF1; NKX2-1; genomic profiling; lineage-specific oncogene; TTF-1; Lung disease; Respiratory disease; Lung cancer; Genomics; Identification; Malignant tumor; Carcinogenesis; Bronchus disease; Onc gene; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1211012

Lung cancer is a leading cause of cancer death, where the amplification of oncogenes contributes to tumorigenesis. Genomic profiling of 128 lung cancer cell lines and tumors revealed frequent focal DNA amplification at cytoband 14q13.3, a locus not amplified in other tumor types. The smallest region of recurrent amplification spanned the homeobox transcription factor TITF1 (thyroid transcription factor 1; also called NKX2-1 ), previously linked to normal lung development and function. When amplified, TITF1 exhibited increased expression at both the RNA and protein levels. Small interfering RNA (siRNA)-mediated knockdown of TITF1 in lung cancer cell lines with amplification led to reduced cell proliferation, manifested by both decreased cell-cycle progression and increased apoptosis. Our findings indicate that TITF1 amplification and overexpression contribute to lung cancer cell proliferation rates and survival and implicate TITF1 as a lineage-specific oncogene in lung cancer.