Horizontal basal cell proliferation in the olfactory epithelium of transforming growth factor-alpha transgenic mice.
Horizontal basal cell proliferation in the olfactory epithelium of transforming growth factor-alpha transgenic mice.
复制标题
转化生长因子-α转基因小鼠嗅觉上皮的水平基底细胞增殖。
DOI：
10.1007/s004419900149
复制
发表时间：
2000
影响因子：
3.6
通讯作者：
Getchell,ML
中科院分区：
文献类型：
--
作者：
Getchell,TV;Narla,RK;Little,S;Hyde,JF;Getchell,ML
用角蛋白14启动子指导转化生长因子α（TGF-α）基因过表达的转基因小鼠研究嗅上皮细胞周期进程和增殖的体内调节。TGF-α蛋白在转基因小鼠鼻嗅上皮中的水平比非转基因同窝对照小鼠高73%。与非转基因组相比，转基因组中TGF-α蛋白水平的增加伴随着表型特征水平基底细胞增殖的5.8倍选择性增加;相反，转基因组和非转基因组中球形基底细胞的增殖水平相似。表皮生长因子受体蛋白（TGF-α受体）的表达水平在转基因动物中也上调，表明ErbB酪氨酸激酶受体家族在嗅上皮对TGF-α的反应中发挥作用。TGF-α过表达还与几种早期细胞周期相关蛋白的表达增加相关，包括生长因子传感器细胞周期蛋白D1、视网膜母细胞瘤、E2 F-1转录因子和细胞周期蛋白E，表明处于细胞周期G1期的相对静止祖细胞向G1/S限制点进展，之后细胞变得对有丝分裂原不敏感。这些结果证明了生长因子TGF-α在这些转基因小鼠中有丝分裂活性嗅上皮细胞周期进展和增殖的体内调节中的作用。
Transgenic mice in which overexpression of the transforming growth factor alpha (TGF-α) gene was directed by the keratin-14 promoter were used to study the regulation of cell cycle progression and proliferation in vivo in the olfactory epithelium. The level of TGF-α protein was 73% greater in the nasal-olfactory epithelium of the transgenic mice than in that of nontransgenic littermate controls. Increased levels of TGF-α protein were accompanied by a 5.8-fold selective increase in the proliferation of phenotypically characterized horizontal basal cells in the transgenics compared with nontransgenics; in contrast, globose basal cells exhibited a similar low level of proliferation in both transgenics and nontransgenics. The level of expression of epidermal growth factor receptor protein, the receptor for TGF-α, was also upregulated in the transgenics, indicating a role for the ErbB tyrosine kinase receptor family in the response to TGF-α in the olfactory epithelium. TGF-α overexpression was also associated with increased expression of several early cell-cycle-associated proteins, including the growth factor sensor cyclin D1, retinoblastoma, E2F-1 transcription factor, and cyclin E, indicating the progression of relatively quiescent progenitor cells in the G1 phase of the cell cycle toward the G1/S restriction point, after which the cells become refractive to mitogens. These results demonstrate a role for the growth factor TGF-α in the in vivo regulation of cell cycle progression and proliferation in the mitotically active olfactory epithelium in these transgenic mice.