The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells
Language: 
English
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.

Author(s): 
Dimri, Goberdhan P.
Martinez, Jose-Luis
Jacobs, Jacqueline J. L.
Keblusek, Petra
Itahana, Koji
Van Lohuizen, Maarten
Campisi, Judith
Wazer, David E.
Band, Vimla
Item Type: 
Journal Article
Publication Title: 
Cancer Research
Journal Abbreviation: 
Cancer Res.
Publication Date: 
8/15/2002
Publication Year: 
2002
Pages: 
4736-4745
Volume: 
62
Issue: 
16
ISSN: 
0008-5472
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 12183433

Turabian/Chicago Citation

Goberdhan P. Dimri, Jose-Luis Martinez, Jacqueline J. L. Jacobs, Petra Keblusek, Koji Itahana, Maarten Van Lohuizen, Judith Campisi, David E. Wazer and Vimla Band. 8/15/2002. "The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells." Cancer Research 62: 16: 4736-4745.

Wikipedia Citation

<ref> {{Cite journal | doi = | issn = 0008-5472 | volume = 62 | pages = 4736-4745 | last = Dimri | first = Goberdhan P. | coauthors = Martinez, Jose-Luis, Jacobs, Jacqueline J. L., Keblusek, Petra, Itahana, Koji, Van Lohuizen, Maarten, Campisi, Judith, Wazer, David E., Band, Vimla | title = The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells | journal = Cancer Research | date = 8/15/2002 | pmid = | pmc = }} </ref>