title: Human telomerase reverse transcriptase mRNA is highly expressed in normal breast tissues and down-regulated in ductal carcinoma in situ.
abstract: Telomerase is a ribonuclear protein that maintains telomere length in eukaryotic cells. Activation of the human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, has been implicated in cellular immortalization and may play a critical role in carcinogenesis. Prior studies in DCIS have been small, and used polymerase chain reaction (PCR)-based methods on heterogeneous tissue extracts. In this study, we used in situ hybridization to determine the cell type and topographic expression pattern of hTERT mRNA in a large series of cased in normal breast ductal-lobular units and ductal carcinoma in situ (DCIS). A total of 120 breast samples were evaluated. High level of hTERT mRNA expression was observed in both normal breast ductal-lobular units and DCIS, which showed a very heterogeneous expression pattern. Overall, hTERT mRNA expression was significantly higher in normal cells compared to DCIS (p=0.000). These results suggest that hTERT not only plays an important role in breast cancer progression but it is also involved in regulating the cellular function of normal breast ductal-lobular units. This finding challenges the conventional view that hTERT mRNA expression is repressed in somatic cells but activated in neoplastic cells. Our results also suggest that telomerase reverse transcriptase mRNA expression may play an important role in the homeostasis of normal breast epithelial cells and neoplastic cells do not necessarily have increased level of expression of hTERT.
authors.affiliation: Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. jliu@mdanderson.org
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.forename: Atac
authors.initials: A
authors.lastname: Baykal
authors.forename: Kar-Ming
authors.initials: KM
authors.lastname: Fung
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Thompson-Lanza
authors.forename: Ashraful
authors.initials: A
authors.lastname: Hoque
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Aysegul
authors.initials: A
authors.lastname: Sahin
mesh_terms: D014408:Biomarkers, Tumor; D001940:Breast / Q000201:enzymology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology* / Q000235:genetics; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017403:In Situ Hybridization; D009361:Neoplasm Invasiveness; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism*; D012334:RNA, Neoplasm; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D015347:RNA Probes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019098:Telomerase