Telomeric protein Pin2/TRF1 induces mitotic entry and apoptosis in cells with short telomeres and is down-regulated in human breast tumors

Shuji Kishi, Gerburg Wulf, Masafumi Nakamura, Kun Ping Lu

Research output: Contribution to journalArticle

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Abstract

Telomeres are essential for cell survival and have been implicated in the mitotic control. The telomeric protein Pin2/TRF1 controls telomere elongation and its expression is tightly regulated during cell cycle. We previously reported that overexpression of Pin2/TRF1 affects mitotic progression. However, the role of Pin2/TRF1 at the interface between cell division and cell survival remains to be determined. Here we show that overexpression of Pin2 induced apoptosis in cells containing short telomeres, but not in cells with long telomeres. Furthermore, before entering apoptosis, Pin2-expressing cells first accumulated in mitosis and strongly stained with the mitosis-specific MPM2 antibody. Moreover, Pin2-induced apoptosis is potentiated by arresting cells in mitosis, but suppressed by accumulating cells in G1. In addition, overexpression of Pin2 also resulted in activation of caspase-3, and its proapoptotic activity was significantly reduced by inhibition of caspase-3. These results indicate that up-regulation of Pin2/TRF1 can specifically induce entry into mitosis and apoptosis, likely via a mechanism related to activation of caspase-3. Significantly, we also found that, out of 51 human breast cancer tissues and 10 normal controls examined, protein levels of Pin2/TRF1 in tumors were significantly lower than in normal tissues, as detected by immunoblotting analysis and immunocytochemistry. Since down-regulation of Pin2/TRF1 allows cells to maintain long telomeres, these results suggest that down-regulation of Pin2/TRF1 may be important for cancer cells to extend their proliferative potential.

Original languageEnglish
Pages (from-to)1497-1508
Number of pages12
JournalOncogene
Volume20
Issue number12
DOIs
Publication statusPublished - Mar 22 2001
Externally publishedYes

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Telomeric Repeat Binding Protein 1
Telomere
Apoptosis
Breast Neoplasms
Mitosis
Caspase 3
Cell Survival
Down-Regulation
Immunoblotting
Cell Division
Neoplasms
Cell Cycle
Up-Regulation
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Telomeric protein Pin2/TRF1 induces mitotic entry and apoptosis in cells with short telomeres and is down-regulated in human breast tumors. / Kishi, Shuji; Wulf, Gerburg; Nakamura, Masafumi; Lu, Kun Ping.

In: Oncogene, Vol. 20, No. 12, 22.03.2001, p. 1497-1508.

Research output: Contribution to journalArticle

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