The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells

Goberdhan P. Dimri, Jose Luis Martinez, Jacqueline J.L. Jacobs, Petra Keblusek, Koji Itahana, Maarten Van Lohuizen, Judith Campisi, David E. Wazer, Vimla Band

Research output: Contribution to journalArticle

299 Citations (Scopus)

Abstract

The vast majority of breast cancers are carcinomas that arise from mammary epithelial cells (MECs). One of the key early events in tumorigenic transformation is the ability of cells to overcome replicative senescence. However, the precise genetic changes that are responsible for this event in MECs is largely unknown. Here, we report that Bmi-1, originally identified as a c-Myc cooperating oncoprotein, can bypass senescence, extend the replicative life span, and immortalize MECs. Furthermore, Bmi-1 was overexpressed in immortal MECs and several breast cancer cell lines. Overexpression of Bmi-1 in MECs led to activation of human telomerase reverse transcriptase (hTERT) transcription and induction of telomerase activity. Telomerase induction by Bmi-1 was an early event in the extension of the replicative life span and immortalization. Bmi-1 was not overexpressed in hTERT-immortalized MECs, suggesting that Bmi-1 functions upstream of hTERT. Although, c-Myc has been reported to induce telomerase in MECs, Bmi-1 appeared to act independently of c-Myc binding sequences in the hTERT promoter. Deletion analysis of the Bmi-1 protein suggested that the RING finger, as well as a conserved helix-turn-helix-turn domain, were required for its ability to induce telomerase and immortalize MECs. These data suggest that Bmi-1 regulates telomerase expression in MECs and plays a role in the development of human breast cancer.

Original languageEnglish (US)
Pages (from-to)4736-4745
Number of pages10
JournalCancer Research
Volume62
Issue number16
StatePublished - Aug 15 2002

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Telomerase
Oncogenes
Human Activities
Breast
Epithelial Cells
Breast Neoplasms
Aptitude
Cell Aging
Neoplastic Cell Transformation
Oncogene Proteins
Human Development
Life Expectancy
Reverse Transcription
Cell Line
human TERT protein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Dimri, G. P., Martinez, J. L., Jacobs, J. J. L., Keblusek, P., Itahana, K., Van Lohuizen, M., ... Band, V. (2002). The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. Cancer Research, 62(16), 4736-4745.

The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. / Dimri, Goberdhan P.; Martinez, Jose Luis; Jacobs, Jacqueline J.L.; Keblusek, Petra; Itahana, Koji; Van Lohuizen, Maarten; Campisi, Judith; Wazer, David E.; Band, Vimla.

In: Cancer Research, Vol. 62, No. 16, 15.08.2002, p. 4736-4745.

Research output: Contribution to journalArticle

Dimri, GP, Martinez, JL, Jacobs, JJL, Keblusek, P, Itahana, K, Van Lohuizen, M, Campisi, J, Wazer, DE & Band, V 2002, 'The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells', Cancer Research, vol. 62, no. 16, pp. 4736-4745.
Dimri GP, Martinez JL, Jacobs JJL, Keblusek P, Itahana K, Van Lohuizen M et al. The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. Cancer Research. 2002 Aug 15;62(16):4736-4745.
Dimri, Goberdhan P. ; Martinez, Jose Luis ; Jacobs, Jacqueline J.L. ; Keblusek, Petra ; Itahana, Koji ; Van Lohuizen, Maarten ; Campisi, Judith ; Wazer, David E. ; Band, Vimla. / The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. In: Cancer Research. 2002 ; Vol. 62, No. 16. pp. 4736-4745.
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