Oncogene-基因文献库-基因云馆

Expression of a rlf/L-myc minigene inhibits differentiation of embryonic stem cells and embroid body formation.

标题

Oncogene

摘要

Rearrangements of the L-myc proto-oncogene with the cellular gene rlf occur in a subset of human small cell lung carcinoma (SCLC) resulting in the expression of a fusion protein. To investigate whether expression of such a rlf/L-myc fusion protein could contribute to the development of SCLC we constructed a chimeric minigene where the rlf first exon and the L-myc second and third exon are under the control of the rlf promoter thereby recapitulating the events of the rearrangement. Attempts to generate transgenic mice with this minigene showed that mouse embryos containing high copy numbers of the rlf/L-myc minigene fail to develop, suggesting that the expression of a rlf/L-myc fusion protein interferes with early differentiation processes. To investigate the nature of this potential embryonic lethality further, we transfected the rlf/L-myc construct stably into embryonic stem (ES) cells. Transfected ES lines that express the rlf/L-myc construct do not show a higher proliferation rate than the parental ES line but fail to properly develop embroid bodies. In addition, outgrowth and differentiation of cells from embroid bodies was severely impaired in ES cells expressing the rlf/L-myc construct when compared to normal ES cells, again suggesting an interference of rlf/L-myc expression with proper differentiation. Expression of a rlf/L-myc fusion may therefore be of critical importance in tumorigenesis by blocking differentiation and thereby allowing continued proliferation of cells and the acquisition of further mutations leading to a fully malignant tumor.

作者

MacLean-Hunter(S),Mäkelä(T P),Grzeschiczek(A),Alitalo(K),Möröy(T)

来源杂志

Oncogene

首次收录时间

1994-12-20

最后更新时间

2007-11-15

issue

volume

iSOAbbreviation

Oncogene

出版商

ppublish

来源国家

England

Expression of a rlf/L-myc minigene inhibits differentiation of embryonic stem cells and embroid body formation.

联系方式

微信公众号