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

ABSTRACT: 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.

SUBMITTER: Kwei KA

PROVIDER: S-EPMC2903002 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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

Kwei K A KA Kim Y H YH Girard L L Kao J J Pacyna-Gengelbach M M Salari K K Lee J J Choi Y-L YL Sato M M Wang P P Hernandez-Boussard T T Gazdar A F AF Petersen I I Minna J D JD Pollack J R JR

Oncogene 20080121 25

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 amplif ...[more]

PMID: 18212743

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Project description:Summary: 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 (also known as NKX2-1), previously linked to normal lung development and function. When amplified, TITF1 exhibited increased expression at both the RNA and protein level. 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. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Cell Line Keywords: Logical Set cDNA microarrays from the Stanford Functional Genomics Facility were used to perform array based Comparative Genomic Hybridization (aCGH) analysis on 52 non-small cell lung cancer (NSCLC) cell lines and 76 NSCLC tumors (36 adenocarcinomas including 2 metastases, and 40 squamous cell carcinomas including 1 metastasis). In addition, this dataset includes 6 immortalized and 3 non-immortalized lung epithelial cell lines and 1 male vs. female genomic DNA for hybridization control. Map positions for arrayed cDNA clones were assigned using the NCBI genome assembly, accessed through the UCSC genome browser database (NCBI Build 36). The most frequent focal DNA amplification not associated with a previously known oncogene occurred at cytoband 14q13.3 where TITF1 resides. The sample labeled normal is a "Normal male vs.female DNA" comparison; the samples: SAEC, HBEC3-UI, HBEC5-UI, HBEC2-KT, HBEC3-KT, HBEC4-KT, HBEC5-KT, HBEC2-E, BEAS-2B are Normal lung epithelial cell lines; samples starting with L are all Lung tumor samples and all the rest are Lung cancer cell lines. Computed

Dataset Information

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

Publications

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

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