Expression of mRNAs for telomeric repeat binding factor (TRF)-1 and TRF2 in atypical adenomatous hyperplasia and adenocarcinoma of the lung.
OBJECTIVE
It has been suggested that atypical adenomatous hyperplasia (AAH) may be a precursor of peripheral adenocarcinoma of the lung. Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto chromosomal ends. Its activity is thought to participate in the development of most human cancers. Telomere-specific DNA-binding proteins, such as telomeric repeat binding factor 1 and telomeric repeat binding factor 2, also control telomere length in a complex interplay with telomerase. Here we investigated the expressions of the mRNAs encoded by the TERF1 and TERF2 genes using in situ hybridization in surgically resected specimens [28 AAHs (11 lesions were interpreted as low-grade AAH, and 17 were interpreted as high-grade AAH) and 40 peripherally located bronchioloalveolar carcinoma (BAC).


RESULTS
A clear overexpression of these mRNAs was recognized in low- and high-grade AAH and BAC samples (as compared with normal tissues) using in situ hybridization and these mRNAs were detected in normal AAH and BAC samples using reverse transcription-PCR. The expressions of TERF1 and TERF2 mRNA detected by in situ hybridization were scored positive in 36% and 82% of low-grade AAH, 65% and 83% of high-grade AAH, and 88% and 88% of BAC, respectively. Statistically significant differences in TERF1 mRNA expression could be shown between low-grade AAH and BAC and between high-grade AAH and BAC. There was no statistical difference in the positive expressions of TERF2 mRNA among low-grade AAH, high-grade AAH, and BAC.


CONCLUSIONS
These results are consistent with (but are not enough to confirm) the idea that high-grade AAH is closely related to BAC.
Nakanishi
Kuniaki
K
Division of Environmental Medicine, National Defense Medical College Research Institute, Tokorozawa 359-8513, Japan.
Kawai
Toshiaki
T
Kumaki
Fumiyuki
F
Hiroi
Sadayuki
S
Mukai
Makio
M
Ikeda
Eiji
E
Koering
Catherine Elaine
CE
Gilson
Eric
E
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism*; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035321:Telomeric Repeat Binding Protein 1 / Q000096:biosynthesis*; D035341:Telomeric Repeat Binding Protein 2 / Q000096:biosynthesis*; D013696:Temperature
D012333:RNA, Messenger; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2