Immortalization of mouse myogenic cells can occur without loss of p16INK4a, p19ARF, or p53 and is accelerated by inactivation of Bax

BMC Cell Biology

Jeffrey Boone Miller¹  Janice A Dominov¹  Amanda J Kravetz¹  Christine A Kostek¹  Mahasweta Girgenrath¹  Jonathan Malowitz¹  Jonathan A Nowak¹ 

[1] Boston Biomedical Research Institute 64 Grove Street Watertown, Massachusetts 02472, USA

关键词: p53;    p19^ARF;    p16^INK4a;    muscle fiber;    myoblast;    Bax;    apoptosis;   

Others  :  1088921
DOI  :  10.1186/1471-2121-5-1

 received in 2003-09-16, accepted in 2004-01-08,  发布年份 2004

【 摘 要 】

Background

Upon serial passaging of mouse skeletal muscle cells, a small number of cells will spontaneously develop the ability to proliferate indefinitely while retaining the ability to differentiate into multinucleate myotubes. Possible gene changes that could underlie myogenic cell immortalization and their possible effects on myogenesis had not been examined.

Results

We found that immortalization occurred earlier and more frequently when the myogenic cells lacked the pro-apoptotic protein Bax. Furthermore, myogenesis was altered by Bax inactivation as Bax-null cells produced muscle colonies with more nuclei than wild-type cells, though a lower percentage of the Bax-null nuclei were incorporated into multinucleate myotubes. In vivo, both the fast and slow myofibers in Bax-null muscles had smaller cross-sectional areas than those in wild-type muscles. After immortalization, both Bax-null and Bax-positive myogenic cells expressed desmin, retained the capacity to form multinucleate myotubes, expressed p19^ARF protein, and retained p53 functions. Expression of p16^INK4a, however, was found in only about half of the immortalized myogenic cell lines.

Conclusions

Mouse myogenic cells can undergo spontaneous immortalization via a mechanism that can include, but does not require, loss of p16^INK4a, and also does not require inactivation of p19^ARF or p53. Furthermore, loss of Bax, which appears to be a downstream effector of p53, accelerates immortalization of myogenic cells and alters myogenesis.

【 授权许可】

   
2004 Nowak et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

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