title: Breast field cancerization: isolation and comparison of telomerase-expressing cells in tumor and tumor adjacent, histologically normal breast tissue.
abstract: Telomerase stabilizes chromosomes by maintaining telomere length, immortalizes mammalian cells, and is expressed in more than 90% of human tumors. However, the expression of human telomerase reverse transcriptase (hTERT) is not restricted to tumor cells. We have previously shown that a subpopulation of human mammary epithelial cells (HMEC) in tumor-adjacent, histologically normal (TAHN) breast tissues expresses hTERT mRNA at levels comparable with levels in breast tumors. In the current study, we first validated a reporter for measuring levels of hTERT promoter activity in early-passage HMECs and then used this reporter to compare hTERT promoter activity in HMECs derived from tumor and paired TAHN tissues 1, 3, and 5 cm from the tumor (TAHN-1, TAHN-3, and TAHN-5, respectively). Cell sorting, quantitative real-time PCR, and microarray analyses showed that the 10% of HMECs with the highest hTERT promoter activity in both tumor and TAHN-1 tissues contain more than 95% of hTERT mRNA and overexpress many genes involved in cell cycle and mitosis. The percentage of HMECs within this subpopulation showing high hTERT promoter activity was significantly reduced or absent in TAHN-3 and TAHN-5 tissues. We conclude that the field of "normal tissue" proximal to the breast tumors contains a population of HMECs similar in hTERT expression levels and in gene expression to the HMECs within the tumor mass and that this population is significantly reduced in tissues more distal to the tumor.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, MSC08 4670 Albuquerque, New Mexico 87131, USA.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Trujillo
authors.forename: William C
authors.initials: WC
authors.lastname: Hines
authors.forename: Keith M
authors.initials: KM
authors.lastname: Vargas
authors.forename: Anna C
authors.initials: AC
authors.lastname: Jones
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Joste
authors.forename: Marco
authors.initials: M
authors.lastname: Bisoffi
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Griffith
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D046228:Microarray Analysis; D008938:Mitosis / Q000235:genetics; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
chemical_list: D019098:Telomerase