Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers.
Allelic loss on the short arm of chromosome 3 is one of the most common events in the pathogenesis of lung cancer. The lactotransferrin gene (LTF, also referred to as the lactoferrin gene, LF) is located at 3p21.3 common eliminated region 1, which is frequently deleted in lung and other cancers. The expression of the LTF gene was absent in 16 (59%) of 27 small cell lung cancer cell lines, 33 (77%) of 43 nonsmall-cell lung cancer (NSCLC) cell lines and 7 (54%) of 13 primary NSCLC, while LTF mRNA was overexpressed in 3 (7%) of 43 NSCLC cell lines. Its expression was restored by treatment with 5-aza-2'-deoxycytidine (5-aza-dC), trichostatin A (TSA) or a combination of both in a subset of lung cancer cell lines without LTF expression. In addition, we found 8 different types of nucleotide substitutions and one frameshift mutation. These results indicate that the LTF gene is inactivated by genetic and epigenetic mechanisms in lung cancer.
Iijima
Hironobu
H
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Tomizawa
Yoshio
Y
Iwasaki
Yasuki
Y
Sato
Koji
K
Sunaga
Noriaki
N
Dobashi
Kunio
K
Saito
Ryusei
R
Nakajima
Takashi
T
Minna
John D
JD
Mori
Masatomo
M
D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D044127:Epigenesis, Genetic; D016368:Frameshift Mutation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007781:Lactoferrin / Q000096:biosynthesis* / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014407:Tumor Cells, Cultured
D007781:Lactoferrin