Relative expression of the RET9 and RET51 isoforms in human pheochromocytomas.
Activating mutations of the RET oncogene cause the inheritance of multiple endocrine neoplasia type 2 (MEN2). The RET pre-mRNA is spliced into several transcripts coding for multiple isoforms, including Ret9 and Ret51. When harboring activating mutations in the cytoplasmic region, the Ret51 protein displays a higher in vitro transforming efficiency as compared to the corresponding Ret9 isoform. We investigated whether a more transforming isoform was preferentially expressed in MEN2 tumors as compared to normal tissues or sporadic pheochromocytomas. By quantitative RNases protection assays, we measured the absolute abundance of the 3' splice variants in pheochromocytomas and in normal tissues. The proportion of RET51 transcripts was highly dispersed between tumors and normal tissues. In familial tumors the proportion of RET51 transcripts was significantly larger (48.1%) than in sporadic tumors (36.75%). This result suggests that the preferential expression of the Ret51 protein isoform, even though moderate, is a growth advantage for MEN2 tumors.
Le Hir
H
H
Centre de G¿en¿etique Mol¿eculaire, Laboratoire associ¿e ¿a l'Universit¿e Pierre et Marie Curie, Gif-sur-Yvette, France.
Charlet-Berguerand
N
N
Gimenez-Roqueplo
A
A
Mannelli
M
M
Plouin
P
P
de Franciscis
V
V
Thermes
C
C
D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D007536:Isomerism; D018813:Multiple Endocrine Neoplasia Type 2a / Q000378:metabolism*; D018814:Multiple Endocrine Neoplasia Type 2b / Q000378:metabolism*; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret; D015347:RNA Probes; D012326:RNA Splicing; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D015347:RNA Probes; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila