Isolation and characterization of four alternate c-erbB3 transcripts expressed in ovarian carcinoma-derived cell lines and normal human tissues

Oncogene. 1998 Jun 25;16(25):3243-52. doi: 10.1038/sj.onc.1201866.


ErbB-3 is a member of the epidermal growth factor receptor (EGFR/ErbB) family. In addition to the previously reported 6.2 kb full-length and 1.4 kb truncated c-erbB3 transcripts, we have observed a 1.7 kb c-erbB3 human transcript in Northern blots that specifically hybridizes to a probe of the extracellular domain of the receptor. Using 3'-RACE we have isolated four novel c-erbB3 cDNA clones of 1.6, 1.7, 2.1 and 2.3 kb from a human ovarian carcinoma-derived cell line. All four alternate transcripts are synthesized by readthrough of an intron and use of an alternative polyadenylation signal within this intron. Identical c-erbB3 transcripts are expressed in normal human placental tissues. Expression of these alternate transcripts is tissue-specific as indicated by Northern blot and RNase protection analyses. Fibroblasts transfected with expression vectors carrying these alternate c-erbB3 cDNA clones stably express truncated ErbB-3 products. Three of these four cDNA clones express a receptor product that is secreted. Immunoprecipitation analysis of primary cultures of human ovarian carcinomas also demonstrate the expression of a 90 kDa ErbB-3 related protein that is secreted. Furthermore, we demonstrate conservation of the exon-intron junctions between members of the erbB gene family in those regions of the gene encoding the extracellular domain. This gene structure is also conserved in the c-erbB1 homologues of Drosophila and C. elegans. Growth regulatory roles for related truncated ErbB products recently have been reported. It is, therefore, possible that the products of these four alternate c-erbB3 transcripts may also play important growth regulatory roles in normal and transformed cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • Culture Media, Conditioned / chemistry
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • ErbB Receptors / analysis
  • ErbB Receptors / genetics*
  • ErbB Receptors / isolation & purification*
  • Eukaryotic Cells / chemistry
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism
  • Exons / genetics
  • Female
  • Gene Expression / genetics
  • Gene Library
  • Humans
  • Molecular Sequence Data
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / genetics*
  • Ovary / cytology*
  • Ovary / metabolism
  • Ovary / pathology
  • Placenta / chemistry
  • Placenta / metabolism
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / isolation & purification*
  • Receptor, ErbB-3
  • Ribonucleases / metabolism
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Transcription, Genetic / genetics
  • Tumor Cells, Cultured


  • Culture Media, Conditioned
  • DNA, Complementary
  • Proto-Oncogene Proteins
  • ErbB Receptors
  • Receptor, ErbB-3
  • Ribonucleases

Associated data

  • GENBANK/U88357
  • GENBANK/U88358
  • GENBANK/U88359
  • GENBANK/U88360