title: Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells.
abstract: The purpose of this study was to determine whether production of liver metastasis by human colon carcinoma (HCC) cells depends on the response of tumor cells to organ-derived growth factors. HCC cells were isolated from several surgical specimens whose malignant potential differed (Dukes' stage B or D tumors), adapted to grow in culture, and assessed for expression of the epidermal growth factor receptor (EGF-R). Northern blot analyses revealed that highly metastatic HCC cells expressed >5-fold the number of EGF-R mRNA transcripts as low metastatic cells. The level of mRNA correlated with the amount of EGF-R protein as detected by Western blotting, immunohistochemistry, and Scatchard analyses. HCC growth response in vitro to picograms of transforming growth factor alpha was associated with functional cell surface EGF-Rs as determined by receptor tyrosine kinase activity assays. The EGF-R gene was not amplified or rearranged in highly metastatic cells. However, fluorescence in situ hybridization analysis showed that the copy number of chromosome 7 was higher in the highly metastatic cells. HCC cells were selected in vitro for low or high expression of EGF-R. Subsequent to injection into nude mice, only cells with high expression of EGF-R produced a high incidence of liver metastasis. These data demonstrate that expression of EGF-R by HCC cells directly correlates with their ability to produce hepatic metastasis.
authors.affiliation: Department of Cell Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: R
authors.initials: R
authors.lastname: Radinsky
authors.forename: S
authors.initials: S
authors.lastname: Risin
authors.forename: D
authors.initials: D
authors.lastname: Fan
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.forename: D
authors.initials: D
authors.lastname: Bielenberg
authors.forename: C D
authors.initials: CD
authors.lastname: Bucana
authors.forename: I J
authors.initials: IJ
authors.lastname: Fidler
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell; D002455:Cell Division / Q000187:drug effects; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D016211:Transforming Growth Factor alpha / Q000494:pharmacology / Q000502:physiology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors