Identification of a novel homeobox-containing gene, LAGY, which is downregulated in lung cancer.
We have isolated a novel gene, lung cancer-associated gene Y (LAGY), by suppression subtractive hybridization. The nucleotide sequence of LAGY predicts a small protein of 73 amino acids containing a putative homeobox domain with a molecular mass of 8.1 kD. Multiple-tissue Northern blot analysis revealed that LAGY is present in human placenta, lung, brain, heart and skeletal muscle. Gene mapping locates LAGY on chromosome 4q11-13.1. The expression of LAGY mRNA was widely lost in 18 lung tumor cell lines comprising all major histological types, as shown by Northern blot analysis and semiquantitative reverse transcription-polymerase chain reaction. In an investigation of 72 primary lung tumors, this gene was significantly downregulated in tumors compared to 9 normal lung tissue samples. There was a significant reduction of LAGY expression in squamous cell carcinoma (SCC; n = 27) with increasing grade and stage. No expression was detectable in two high-grade SCCs or two small cell and large cell lung carcinomas (n = 4 for each). In adenocarcinoma (n = 37), expression was reduced; however, this did not reach statistical significance. Since homeodomain-containing genes are known to transcriptionally regulate key cellular processes and are associated with carcinogenesis, we suggest that LAGY might be linked to lung cancer development and progression.
Chen
Yuan
Y
Institute of Pathology, University Hospital Charité, Berlin, Germany.
Petersen
Simone
S
Pacyna-Gengelbach
Manuela
M
Pietas
Agnieszka
A
Petersen
Iver
I
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis; D004273:DNA, Neoplasm / Q000032:analysis; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm