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

Hakjoo Lee, Nita J. Maihle

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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 ErbB3 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.

Original languageEnglish (US)
Pages (from-to)3243-3252
Number of pages10
JournalOncogene
Volume16
Issue number25
DOIs
StatePublished - Jun 25 1998

Keywords

  • Alternative processing
  • Epidermal growth factor receptor homologues
  • Gene structure
  • Truncated growth factor receptors
  • c-erbB3

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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