Human Renal Carcinoma Expresses Two Messages Encoding a Parathyroid Hormone-Like Peptide: Evidence for the Alternative Splicing of a Single-Copy Gene

• Published in: Proceedings of the National Academy of Sciences - PNAS 1988-07, Vol.85 (13), p.4605-4609
• Main Authors: Thiede, Mark A., Strewler, Gordon J., Nissenson, Robert A., Rosenblatt, Michael, Rodan, Gideon A.
• Format: Article
• Language: English
• Subjects: 550201 - Biochemistry- Tracer Techniques; Alternative splicing; AMINO ACID SEQUENCE; Amino acids; ANIMALS; Base Sequence; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; Biological and medical sciences; BODY; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; CARCINOMAS; Cell lines; Chemical bases; Complementary DNA; DAYS LIVING RADIOISOTOPES; DISEASES; DNA; DNA - genetics; DNA SEQUENCING; Fundamental and applied biological sciences. Psychology; Gene expression; GENES; GLANDS; HORMONES; Hormones, Ectopic - genetics; Humans; HYBRIDIZATION; ISOTOPES; KIDNEYS; LIGHT NUCLEI; LUNGS; MAMMALS; MAMMARY GLANDS; MAN; MESSENGER-RNA; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; MOLECULAR STRUCTURE; NEOPLASMS; NUCLEI; NUCLEIC ACIDS; ODD-ODD NUCLEI; OLIGONUCLEOTIDES; ORGANIC COMPOUNDS; ORGANS; Paraneoplastic Endocrine Syndromes - genetics; Paraneoplastic Endocrine Syndromes - pathology; PARATHORMONE; Parathyroid Hormone - genetics; Parathyroid neoplasms; PEPTIDE HORMONES; PEPTIDES; Peptides - genetics; PHOSPHORUS 32; PHOSPHORUS ISOTOPES; PRIMATES; PROTEINS; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-myc; PURIFICATION; RADIOISOTOPES; RECOMBINANT DNA; RESPIRATORY SYSTEM; RNA; RNA Splicing; RNA, Messenger - genetics; RNA, Neoplasm - genetics; SECRETION; STRUCTURAL CHEMICAL ANALYSIS; Tumor cell line; Tumor Cells, Cultured; VERTEBRATES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.13.4605

A peptide secreted by tumors associated with the clinical syndrome of humoral hypercalcemia of malignancy was recently purified from human renal carcinoma cell line 786-0. The N-terminal amino acid sequence of this peptide has considerable similarity with those of parathyroid hormone (PTH) and of peptides isolated from human breast and lung carcinoma (cell line BEN). In this study we obtained the nucleotide sequence of a 1595-base cDNA complementary to mRNA encoding the PTH-like peptide produced by 786-0 cells. The cDNA contains an open reading frame encoding a leader sequence of 36 amino acids and a 139-residue peptide, in which 8 of the first 13 residues are identical to the N terminus of PTH. Through the first 828 bases the sequence of this cDNA is identical with one recently isolated from a BEN cell cDNA library; however, beginning with base 829 the sequences diverge, shortening the open reading frame by 2 amino acids. Differential RNA blot analysis revealed that 786-0 cells express two major PTH-like peptide mRNAs with different 3′ untranslated sequences, one of which hybridizes with the presently described sequence and the other one with that reported for the BEN cell PTH-like peptide cDNA. Primer-extension analysis of 786-0 poly(A)+ RNA together with Southern blot analysis of human DNA confirmed the presence of a single-copy gene coding for multiple mRNAs through alternate splicing. In addition, the 3′ untranslated sequence of the cDNA described here has significant similarity to the c-myc protooncogene.