Telomerase activity and its inhibition in benign and malignant breast lesions

Takashi Sugino, Kazuhiro Yoshida, John Bolodeoku, David Tarin, Steve Goodison

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Many types of human tumours and immortal cell lines have been demonstrated to exhibit telomerase activity with the recently formulated telomeric repeat amplification protocol (TRAP assay). However, a small proportion of undoubted tumour samples give a negative result and it has been postulated that, on occasion, the assay can be blocked by inhibitory factors in the cell or tissue extracts. To resolve this issue, a modified TRAP assay has been used to re-examine 45 previously negative breast tissue specimens. Phenol-chloroform extraction of the sample after the telomerase extension reaction revealed the presence of polymerase chain reaction (PCR) inhibitory factors in tissue from 6 of 14 (43 per cent) breast biopsies of fibrocystic disease (FCD), 6 of 12 (50 per cent) fibroadenomas (FAs), none of live carcinomas in situ, and 1 of 13 (8 per cent) invasive carcinoma (CA) tissue specimens. These results demonstrated that the enzyme telomerase can be active in some benign lesions as well as in carcinomas of the breast. Specimens which still remained negative for telomerase in the above experiment were next assayed for the presence of biologically relevant inhibitors of the enzyme by mixing the extracts with confirmed positive samples. Extracts from 12 of 17 carcinoma specimens (all of five carcinomas in situ and 7 of 12 invasive carcinomas showed dose-dependent inhibitory activity against telomere extension, whereas no inhibition was observed in those of three of eight FCD and 2 of seven FAs. These results indicate that telomerase activity may be regulated by a balance between inhibitory factors and an activated enzyme.

Original languageEnglish (US)
Pages (from-to)57-61
Number of pages5
JournalJournal of Pathology
Volume183
Issue number1
DOIs
StatePublished - Sep 1 1997

Keywords

  • Breast cancer
  • Telomerase assay
  • Telomerase inhibitors
  • Telomerase regulation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Telomerase activity and its inhibition in benign and malignant breast lesions'. Together they form a unique fingerprint.

  • Cite this