期刊
BMC CELL BIOLOGY
卷 5, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2121-5-1
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资金
- NHLBI NIH HHS [R01 HL064641, HL064641] Funding Source: Medline
- NIAMS NIH HHS [AR049496, R21 AR049306, R01 AR049496, AR049306] Funding Source: Medline
- NIEHS NIH HHS [U19 ES011384, ES011384] Funding Source: Medline
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 p16INK4a, and also does not require inactivation of p19ARF or p53. Furthermore, loss of Bax, which appears to be a downstream effector of p53, accelerates immortalization of myogenic cells and alters myogenesis.
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