Inactivation of LLC1 gene in nonsmall cell lung cancer.
Serial analysis of gene expression studies led us to identify a previously unknown gene, c20orf85, that is present in the normal lung epithelium but absent or downregulated in most primary nonsmall cell lung cancers and lung cancer cell lines. We named this gene LLC1 for Low in Lung Cancer 1. LLC1 is located on chromosome 20q13.3 and has a 70% GC content in the promoter region. It has 4 exons and encodes a protein containing 137 amino acids. By in situ hybridization, we observed that LLC1 message is localized in normal lung bronchial epithelial cells but absent in 13 of 14 lung adenocarcinoma and 9 out of 10 lung squamous carcinoma samples. Methylation at CpG sites of the LLC1 promoter was frequently observed in lung cancer cell lines and in a fraction of primary lung cancer tissues. Treatment with 5-aza deoxycytidine resulted in a reduced methylation of the LLC1 promoter concomitant with the increase of LLC1 expression. These results suggest that inactivation of LLC1 by means of promoter methylation is a frequent event in nonsmall cell lung cancer and may play a role in lung tumorigenesis.
Hong
Kyeong-Man
KM
Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yang
Sei-Hoon
SH
Chowdhuri
Sinchita Roy
SR
Player
Audrey
A
Hames
Megan
M
Fukuoka
Junya
J
Meerzaman
Daoud
D
Dracheva
Tatiana
T
Sun
Zhifu
Z
Yang
Ping
P
Jen
Jin
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002417:Cattle; D017931:DNA Primers; D004285:Dogs; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D011506:Proteins; C520369:CIMIP1 protein, human