Abstract

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. Tissuespecific 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. 1 This work was supported by Grant SA023 from the Council for Tobacco Research, USA, Inc., the American Lung Association, the American Gastroenterological Association Foundation, The Elsa U. Pardee Foundation, and NIH Grant CA-63507. 2 To whom requests for reprints should be addressed, at Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, 3110 Medical Sciences Building, 231 Bethesda Avenue, Cincinnati, OH 45267.