Involvement of LIM domain proteins and Lbd2 in the lung tissue development and carcinogensis.

我们之前分离了人类LIMK2基因，并鉴定了两个替代转录本，LIMK2a和LIMK2b，它们以组织特异性的方式进行差异调节。为了研究这一机制及其涉及的转录因子，我们分离了LIMK2a和2b启动子。荧光素酶的转录活性报告分析显示，两个启动子内都有阳性和阴性的调控区域。共转染实验表明，转录因子MZF-1可能以不同的方式调节LIMK2亚型的表达。核受体r α1可能也参与了LIMK2b亚型的转录调控。这些发现将有助于更好地理解LIMK家族可能具有的多种功能。我们还分离并研究了Ldb2基因。Ldb2对核LIM蛋白具有很强的结合特异性，被认为参与了转录调控。研究了Ldb2及其同系物Ldb1的表达模式。Ldb2在正常肺中优先表达，而Ldb1在肺癌组织中表达增加，提示这两个基因在肺癌发生中的差异参与。我们还检测了Ldb2基因在肺癌细胞系中的地位。然而，我们没有发现任何基因改变。

We previously isolated the human LIMK2 gene and identified two alternative transcripts, LIMK2a and LIMK2b, which were differentially regulated in a tissue-specific manner. To investigate this mechanism and the transcription factors involved, we isolated the LIMK2a and 2b promoters. A luciferase reporter assay of the transcriptional activity revealed positive as well as negative regulatory regions within both promoters. The co-transfection assay suggested that the transcription factor, MZF-1, might regulate the expression of the LIMK2 isoforms in a different manner. The nuclear recptor, RORα1, might also be involved in the transcriptional regulation of the LIMK2b isoform. These findings should lead to a better understanding of the possibly diverse functions of the LIMK family.We also isolated and studied the Ldb2 gene. The Ldb2 had the strong binding specificity to nuclar LIM proteins, which were thought to be involeved in the transcriptional regulation. The expression pattern of Ldb2 and its homologue Ldb1 were studied. The Ldb2 is expressed preferentially in normal lung, while the Ldb1 expression is increased in lung cancer tissues, suggesting the differential involvement of these genes in lung carcinogensis. We also examined the status of the Ldb2 gene in lung cancer cell lines. However, we could not find any genetic alteration.