Expression of RET 3′ splicing variants during human kidney development

Abstract

The mature mammalian kidney arises through a series of reciprocal inductive interactions between two di erent cell groups, the ureteric bud epithelium and the metanephric mesenchyme. The RET receptor tyrosine kinase is required for induction and development of the metanephric kidney. Di erential splicing at the 3' end of RET results in transcripts encoding three isoforms that di er with respect to their C-terminal 9 (RET9), 51 (RET51) or 43 (RET43) amino acids. In vitro assays have identi®ed di erences in the abilities of the RET9 and RET51 isoforms to induce di erentiation suggesting functional di erences between these proteins. We examined the relative expression levels of the three RET 3' splicing variants in developing human kidney using semi-quantitative RT ± PCR. We observed consistent expression of the RET9 and RET43 variants in kidney samples spanning 7.5 through 24 weeks gestation. At early gestational ages (7.5 ± 8.5 weeks), RET51 expression was very low (+5%) compared to RET9; however, a rapid seven fold increase in expression was detected by 9 weeks. Our data suggest that RET51 may contribute to di erentiation-related events occurring after 8.5 weeks gestation rather than to induction of the human kidney.

Activation of Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated Kinase Is Required for Glial Cell Line-Derived Neurotrophic Factor-Induced Migration and Invasion of Pancreatic Carcinoma Cells

“…Exon 19 is spliced to exon 20 in RET51 mRNA and to exon 21 in RET43 mRNA. In RET9 mRNA, the intron sequence downstream of exon 19 is transcribed (17,18). RT-PCR analyses with a common 5Ј oligonucleotide binding to a sequence in exon 16 and splice variant-specific 3Ј oligonucleotides demonstrated that mRNAs encoding all three of the RET isoforms were expressed in PANC-1 pancreatic carcinoma cells ( Fig.…”

“…The human ret gene contains 21 exons, and alternative splicing at the 5Ј and 3Ј ends of the RET heterogenous nuclear RNA has been reported (16 -18). The three RET isoforms, RET9, RET43, and RET51, which differ in 9, 43, and 51 amino acids at the COOH terminus, respectively, are produced by alternative splicing in the 3Ј region of exon 19 (17,18). All three of the RET transcripts are coexpressed in human adult tissues and most fetal tissues (16 -18), and the isoforms seem to have different biological functions (19).…”

Expression and alternative splicing of c-ret RNA in papillary thyroid carcinomas

“…ret 3'-splicing variants were also identi®ed (Myers et al, 1995;Ivanchuk et al, 1998). The various ret splicing variants reported may a ect the ligand-interacting or signaling properties of the receptor (Lorenzo et al, 1997;van Weering and Bos, 1998).…”

The Relationship between Over-expression of Glial Cell-derived Neurotrophic Factor and Its RET Receptor with Progression and Prognosis of Human Pancreatic Cancer

“…5,9 The human ret gene contains 21 exons, and alternative splicing at the 5′ and 3′ ends of the RET heterogenous nuclear RNA has been reported. 21 Mutations of the ret protooncogene are responsible for several inherited human diseases and may function as genetic modifiers of disease. Alterations in the gene encoding RET, which forms complexes with the receptors of all the forms of GDNF, are responsible for multiple endocrine neoplasia types 2A and 2B and familial medullary thyroid carcinoma.…”