科研之友
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摘要
As a critical member of the p53 family of transcription factors, p63 has been implicated a role in development than in tumor formation, because p63 is seldom mutated in human cancers, while p63 null mice exhibit severe developmental abnormalities without increasing cancer susceptibility. Notably, besides the major epithelial and cardiac defect, p63 deficient mice show severe limb and craniofacial abnormalities. In addition, humans with p63 mutations also show severe limb and digit defects, suggesting a putative role of p63 in skeletal development. There are eight p63 variants which encode for the TAp63 and Delta Np63 isoforms by alternative promoters. How these isoforms function during skeletal development is currently largely unknown. Our recent transgenic studies suggest a role of TAP63 alpha, but not Delta NP63 alpha, during embryonic long bone development. However, the moderate skeletal phenotypes in the TAP63 alpha transgenic mice suggest requirement of additional p63 isoform(s) for the limb defects in p63 null mice. Here, we report analysis of mouse p63 variants in MCT and ATDC5 cells, two cell models undergo hypertrophic differentiation and mimic the process of endochondral bone formation upon growth arrest or induction. We detected increased level of p63 variants in hypertrophic MCT cells by regular RT-PCR analysis. Further analysis by qRT-PCR, we detected significantly upregulated level of gamma variant (p%26lt; 0.05), but not alpha or beta variant (p%26gt; 0.05), in hypertrophic MCT cells than in proliferative MCT cells. Moreover, we detected upregulated TAP63 gamma in ATDC5 cells undergoing hypertrophic differentiation. Our results suggest that TAp63 gamma plays a positive role during endochondral bone formation.
- 出版日期2013
- 单位江苏大学
