Santoro I M, Groden J
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Ohio 45267, USA.
Cancer Res. 1997 Feb 1;57(3):488-94.
The human tumor suppressor gene, APC, is composed of at least 21 exons, 7 of which are alternatively expressed. Sixteen APC transcripts that differ in their 5'-most regions and arise by the alternative inclusion of 6 of these exons have been identified by reverse transcription-PCR analysis of RNA prepared from human, mouse, and rat cell lines and tissues. Tissue-specific differences were observed in the expression of APC transcripts without exon 1, a coding region for a heptad repeat that supports APC homodimerization. Transcripts without exon 1 were observed at high levels in postmitotic, differentiated tissues and in two cell lines following the induction of differentiation. Sequence analysis of these novel open reading frames predicts APC proteins with different amino-terminal domains and therefore potentially different abilities to associate with other proteins. Our findings suggest that the alternative splicing of APC leads to alternative forms of APC proteins with potentially unique functions in growth control and differentiation.
人类肿瘤抑制基因APC由至少21个外显子组成，其中7个可选择性表达。通过对从人、小鼠和大鼠细胞系及组织中提取的RNA进行逆转录聚合酶链反应分析，已鉴定出16种在其5'端区域不同且由这些外显子中的6个选择性包含而产生的APC转录本。在没有外显子1（支持APC同二聚化的七肽重复序列的编码区）的APC转录本表达中观察到组织特异性差异。在有丝分裂后、分化的组织以及诱导分化后的两个细胞系中，未发现外显子1的转录本水平较高。对这些新开放阅读框的序列分析预测，APC蛋白具有不同的氨基末端结构域，因此可能具有与其他蛋白结合的不同能力。我们的研究结果表明，APC的可变剪接导致了APC蛋白的不同形式，这些形式在生长控制和分化中可能具有独特的功能。
