RUNX3 downregulation in human lung adenocarcinoma is independent of p53, EGFR or KRAS status.
RUNX3 aberrations play a pivotal role in the oncogenesis of breast, gastric, colon, skin and lung tissues. The aim of this study was to characterize further the expression of RUNX3 in lung cancers. To achieve this, a lung cancer tissue microarray (TMA), frozen lung cancer tissues and lung cell lines were examined for RUNX3 expression by immunohistochemistry, while the TMA was also examined for EGFR and p53 expression. RUNX3 promoter methylation status, and EGFR and KRAS mutation status were also investigated. Inactivation of RUNX3 was observed in 70% of the adenocarcinoma samples, and this was associated with promoter hypermethylation but not biased to EGFR/KRAS mutations. Our results suggest a central role of RUNX3 downregulation in pulmonary adenocarcinoma, which may not be dependent of other established cancer-causing pathways and may have important diagnostic and screening implications.
Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, #12-01, 14 Medical Drive, Singapore, 117599, Singapore.
Mohd Feroz Mohd
MF
Omar
Kosei
K
Ito
Min En
ME
Nga
Ross
R
Soo
Bee Keow
BK
Peh
Tuty Muliana
TM
Ismail
Bhavin
B
Thakkar
Richie
R
Soong
Yoshiaki
Y
Ito
Manuel
M
Salto-Tellez
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D050677:Core Binding Factor Alpha 3 Subunit; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C493729:Runx3 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins