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


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 (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 gene expression profiling on 33 non-small cell lung cancer (NSCLC) cell lines, 1 immortalized and 2 non-immortalized lung epithelial cell lines. Mann-Whitney U-Test (p=0.046) was performed to demonstrate that TITF1 increased expression was correlated with TITF1 gene amplification (as shown by aCGH analysis). NHBEC, SAEC and BEAS-2B are Normal lung epithelial cell lines, the others are Lung cancer cell lines Using regression correlation

ORGANISM(S): Homo sapiens

SUBMITTER: Jonathan Pollack 

PROVIDER: E-GEOD-9994 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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]

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