Increased susceptibility to urethane-induced lung tumors in mice with decreased expression of connexin43
Increased susceptibility to urethane-induced lung tumors in mice with decreased expression of connexin43
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DOI：
10.1093/carcin/bgh193
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发表时间：
2004-10-01
期刊：
影响因子：
4.7
通讯作者：
Dagli, MLZ
中科院分区：
文献类型：
--
作者：
Avanzo, JL;Mesnil, M;Dagli, MLZ
据报道，在人类肺癌中，缝隙连接、细胞间通讯能力和连接蛋白的表达降低。缝隙连接蛋白作为肿瘤抑制因子的机制尚不清楚。为了了解连接蛋白在肿瘤发生中的作用，我们分析了Gja1[连接蛋白43(Cx43)基因]的异源缺失在小鼠肺腺瘤发生发展中的作用。杂合子(Cx43(+/-))和野生型(Cx43(+/+))小鼠在出生后15天和17天分别单次注射或不注射乌拉坦。25周后，Cx43(+/-)小鼠的结节数目和大小均较Cx43(+/+)小鼠增多。此外，杂合子小鼠的病变在组织学上更具侵袭性。然而，未经治疗的Cx43(+/-)小鼠肺中的自发病变并未增加。杂合子小鼠有效地表现出Cx43基因的低表达和Cx43的数量减少。总之，我们的结果表明，Cx43基因的一个等位基因的缺失明显有利于乌拉坦的致癌作用，并导致小鼠对肺腺瘤形成的更高易感性。
Gap junction intercellular communication capacity and connexin expression are reportedly decreased in human lung cancer. The mechanisms by which connexins, the gap junction proteins, act as tumor suppressors are unclear. In order to understand the involvement of connexins in tumorigenesis, we analyzed the effect of the heterologous deletion of Gja1 [the connexin43 (Cx43) gene] on the development of lung adenomas in mice. Heterozygous (Cx43(+/-)) and wild-type mice (Cx43(+/+)) were treated or not with single doses of urethane at 15 and 17 days after birth. Twenty-five weeks later, both the number and size of nodules were increased in Cx43(+/-) mice as compared with Cx43(+/+) mice. Moreover, the lesions were histologically more aggressive in the heterozygous mice. However, no increase in spontaneous lesions was observed in the lungs of untreated Cx43(+/-) mice. Heterozygous mice effectively presented lower expression of Cx43 genes and decreased amounts of Cx43. In conclusion, our results indicate that deletion of one allele of the Cx43 gene clearly favors the carcinogenic effect of urethane administration and results in a higher susceptibility to lung adenoma formation in mice.