Expression and Alternative Splicing of the Deleted in Colorectal Cancer (DCC) Gene in Normal and Malignant Tissues

Michael A. Reale, Gang Hu, Abrahim I. Zafar, Robert H. Getzenberg, Stuart M. Levine, Eric R. Fearon

Research output: Contribution to journalArticlepeer-review

Abstract

The DCC (deleted in colorectal cancer) gene was identified because it is affected by somatic mutations in colorectal tumors, including allelic losses in greater than 70% of cancers and localized mutations in a subset of cases. The DCC gene also may be inactivated in other tumor types, including cancers of the pancreas, stomach, breast, prostate, and brain, as well as some leukemias. We have characterized DCC complementary DNAs obtained from human fetal brain tissues and IMR32 human neuroblastoma cells. Based on the fetal brain complementary DNA sequence, the predicted transmembrane DCC protein product has 1447 amino acids. The extracellular domain of about 1100 amino acids has four immunoglobulin-like domains and six fibronectin type Ill-like domains; the 325-amino acid cytoplasmic domain does not show similarity to previously characterized proteins. Comparison of DCC complementary DNAs from IMR32 cells to those from fetal brain identified two potential alternative splice sites. Studies of adult mouse tissues revealed that DCC trancripts were present at very low levels in all tissues studied, and alternative splicing of DCC transcripts was seen in some tissues. Immunoblotting and immunoprecipitation studies with DCC-spedfic antisera identified protein species with molecular weights of approximately 175,000-190,000 in some rodent tissues and human tumor cell lines. DCC protein expression was highest in brain tissues and neural crest-derived cell lines and markedly reduced or absent in the majority of cancer cell lines studied. Treatment of DCC-expressing cells with tunicamydn decreased the apparent molecular weight of the immunoreactive proteins, establishing that DCC is a glycoprotein. The studies presented here demonstrate that the DCC gene encodes several related glycoprotein spedes that are likely to be expressed at very low levels in many normal adult tissues. Furthermore, the absence of DCC expression in some of the cancer cell lines studied may result from genetic inactivation of DCC.

Original languageEnglish (US)
Pages (from-to)4493-4501
Number of pages9
JournalCancer Research
Volume54
Issue number16
StatePublished - Aug 1994

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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