Abstract
Oncogenicity tests have revealed that a nonmutated erbB oncogene induces renal adenocarcinoma in addition to erythroblastosis. The erbB oncogene is a truncated form of the chicken epidermal growth factor receptor that lacks the extracellular ligand-binding domain. Previously, the nonmutated erbB oncogene has been reported to cause only erythroblastosis. The expansion of the disease potential of erbB to additional neoplasms has been associated with mutations (truncations, deletions, and point mutations) within the erbB gene. Our results indicate that a nonmutated virally expressed erbB oncogene (REB-c) causes a 100% incidence of renal neoplasia.
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- Beug H., Hayman M. J., Raines M. B., Kung H. J., Vennström B. Rous-associated virus 1-induced erythroleukemic cells exhibit a weakly transformed phenotype in vitro and release c-erbB-containing retroviruses unable to transform fibroblasts. J Virol. 1986 Mar;57(3):1127–1138. doi: 10.1128/jvi.57.3.1127-1138.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Breyer M. D., Redha R., Breyer J. A. Segmental distribution of epidermal growth factor binding sites in rabbit nephron. Am J Physiol. 1990 Oct;259(4 Pt 2):F553–F558. doi: 10.1152/ajprenal.1990.259.4.F553. [DOI] [PubMed] [Google Scholar]
- CARR J. G. Renal adenocarcinoma induced by fowl leukaemia virus. Br J Cancer. 1956 Jun;10(2):379–383. doi: 10.1038/bjc.1956.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Choi O. R., Trainor C., Graf T., Beug H., Engel J. D. A single amino acid substitution in v-erbB confers a thermolabile phenotype to ts167 avian erythroblastosis virus-transformed erythroid cells. Mol Cell Biol. 1986 May;6(5):1751–1759. doi: 10.1128/mcb.6.5.1751. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Countaway J. L., Nairn A. C., Davis R. J. Mechanism of desensitization of the epidermal growth factor receptor protein-tyrosine kinase. J Biol Chem. 1992 Jan 15;267(2):1129–1140. [PubMed] [Google Scholar]
- Damm K., Beug H., Graf T., Vennström B. A single point mutation in erbA restores the erythroid transforming potential of a mutant avian erythroblastosis virus (AEV) defective in both erbA and erbB oncogenes. EMBO J. 1987 Feb;6(2):375–382. doi: 10.1002/j.1460-2075.1987.tb04765.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Derynck R., Goeddel D. V., Ullrich A., Gutterman J. U., Williams R. D., Bringman T. S., Berger W. H. Synthesis of messenger RNAs for transforming growth factors alpha and beta and the epidermal growth factor receptor by human tumors. Cancer Res. 1987 Feb 1;47(3):707–712. [PubMed] [Google Scholar]
- Fisher D. A., Salido E. C., Barajas L. Epidermal growth factor and the kidney. Annu Rev Physiol. 1989;51:67–80. doi: 10.1146/annurev.ph.51.030189.000435. [DOI] [PubMed] [Google Scholar]
- Freeman M. R., Washecka R., Chung L. W. Aberrant expression of epidermal growth factor receptor and HER-2 (erbB-2) messenger RNAs in human renal cancers. Cancer Res. 1989 Nov 15;49(22):6221–6225. [PubMed] [Google Scholar]
- Frykberg L., Palmieri S., Beug H., Graf T., Hayman M. J., Vennström B. Transforming capacities of avian erythroblastosis virus mutants deleted in the erbA or erbB oncogenes. Cell. 1983 Jan;32(1):227–238. doi: 10.1016/0092-8674(83)90513-5. [DOI] [PubMed] [Google Scholar]
- Gamett D. C., Tracy S. E., Robinson H. L. Differences in sequences encoding the carboxyl-terminal domain of the epidermal growth factor receptor correlate with differences in the disease potential of viral erbB genes. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6053–6057. doi: 10.1073/pnas.83.16.6053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harris R. C. Potential physiologic roles for epidermal growth factor in the kidney. Am J Kidney Dis. 1991 Jun;17(6):627–630. doi: 10.1016/s0272-6386(12)80336-2. [DOI] [PubMed] [Google Scholar]
- Hughes S. H., Greenhouse J. J., Petropoulos C. J., Sutrave P. Adaptor plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors. J Virol. 1987 Oct;61(10):3004–3012. doi: 10.1128/jvi.61.10.3004-3012.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jansson M., Beug H., Gray C., Graf T., Vennström B. Defective v-erbB genes can be complemented by v-erbA in erythroblast and fibroblast transformation. Oncogene. 1987 May;1(2):167–173. [PubMed] [Google Scholar]
- Maihle N. J., Kung H. J. C-erbB and the epidermal growth-factor receptor: a molecule with dual identity. Biochim Biophys Acta. 1989 Feb;948(3):287–304. doi: 10.1016/0304-419x(89)90003-6. [DOI] [PubMed] [Google Scholar]
- Miles B. D., Robinson H. L. High-frequency transduction of c-erbB in avian leukosis virus-induced erythroblastosis. J Virol. 1985 May;54(2):295–303. doi: 10.1128/jvi.54.2.295-303.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mydlo J. H., Michaeli J., Cordon-Cardo C., Goldenberg A. S., Heston W. D., Fair W. R. Expression of transforming growth factor alpha and epidermal growth factor receptor messenger RNA in neoplastic and nonneoplastic human kidney tissue. Cancer Res. 1989 Jun 15;49(12):3407–3411. [PubMed] [Google Scholar]
- Nogueira E., Stumpf H., Rütter G., Llombart-Bosch A., Bannasch P. Cellular and molecular mechanisms of renal carcinogenesis induced by avian erythroblastosis virus. Lab Invest. 1992 Feb;66(2):152–165. [PubMed] [Google Scholar]
- Pelley R. J., Maihle N. J., Boerkoel C., Shu H. K., Carter T. H., Moscovici C., Kung H. J. Disease tropism of c-erbB: effects of carboxyl-terminal tyrosine and internal mutations on tissue-specific transformation. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7164–7168. doi: 10.1073/pnas.86.18.7164. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pelley R. J., Moscovici C., Hughes S., Kung H. J. Proviral-activated c-erbB is leukemogenic but not sarcomagenic: characterization of a replication-competent retrovirus containing the activated c-erbB. J Virol. 1988 May;62(5):1840–1844. doi: 10.1128/jvi.62.5.1840-1844.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Petrides P. E., Bock S., Bovens J., Hofmann R., Jakse G. Modulation of pro-epidermal growth factor, pro-transforming growth factor alpha and epidermal growth factor receptor gene expression in human renal carcinomas. Cancer Res. 1990 Jul 1;50(13):3934–3939. [PubMed] [Google Scholar]
- Raines M. A., Maihle N. J., Moscovici C., Moscovici M. G., Kung H. J. Molecular characterization of three erbB transducing viruses generated during avian leukosis virus-induced erythroleukemia: extensive internal deletion near the kinase domain activates the fibrosarcoma- and hemangioma-inducing potentials of erbB. J Virol. 1988 Jul;62(7):2444–2452. doi: 10.1128/jvi.62.7.2444-2452.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robinson H. L., Astrin S. M., Senior A. M., Salazar F. H. Host Susceptibility to endogenous viruses: defective, glycoprotein-expressing proviruses interfere with infections. J Virol. 1981 Dec;40(3):745–751. doi: 10.1128/jvi.40.3.745-751.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robinson H. L., Tracy S. E., Nair N., Taglienti-Sian C., Gamett D. C. Characterization of an angiosarcoma-inducing mutation in the erbB oncogene. Oncogene. 1992 Oct;7(10):2025–2030. [PubMed] [Google Scholar]
- Sargent E. R., Gomella L. G., Belldegrun A., Linehan W. M., Kasid A. Epidermal growth factor receptor gene expression in normal human kidney and renal cell carcinoma. J Urol. 1989 Nov;142(5):1364–1368. doi: 10.1016/s0022-5347(17)39100-0. [DOI] [PubMed] [Google Scholar]
- Sealy L., Moscovici G., Moscovici C., Bishop J. M. Site-specific mutagenesis of avian erythroblastosis virus: v-erb-A is not required for transformation of fibroblasts. Virology. 1983 Oct 15;130(1):179–194. doi: 10.1016/0042-6822(83)90126-5. [DOI] [PubMed] [Google Scholar]
- Sealy L., Privalsky M. L., Moscovici G., Moscovici C., Bishop J. M. Site-specific mutagenesis of avian erythroblastosis virus: erb-B is required for oncogenicity. Virology. 1983 Oct 15;130(1):155–178. doi: 10.1016/0042-6822(83)90125-3. [DOI] [PubMed] [Google Scholar]
- Shu H. K., Pelley R. J., Kung H. J. Dissecting the activating mutations in v-erbB of avian erythroblastosis virus strain R. J Virol. 1991 Nov;65(11):6173–6180. doi: 10.1128/jvi.65.11.6173-6180.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shu H. K., Pelley R. J., Kung H. J. Tissue-specific transformation by epidermal growth factor receptor: a single point mutation within the ATP-binding pocket of the erbB product increases its intrinsic kinase activity and activates its sarcomagenic potential. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9103–9107. doi: 10.1073/pnas.87.23.9103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Theroux S. J., Latour D. A., Stanley K., Raden D. L., Davis R. J. Signal transduction by the epidermal growth factor receptor is attenuated by a COOH-terminal domain serine phosphorylation site. J Biol Chem. 1992 Aug 15;267(23):16620–16626. [PubMed] [Google Scholar]
- Theroux S. J., Taglienti-Sian C., Nair N., Countaway J. L., Robinson H. L., Davis R. J. Increased oncogenic potential of ErbB is associated with the loss of a COOH-terminal domain serine phosphorylation site. J Biol Chem. 1992 Apr 25;267(12):7967–7970. [PubMed] [Google Scholar]
- Tracy S. E., Woda B. A., Robinson H. L. Induction of angiosarcoma by a c-erbB transducing virus. J Virol. 1985 May;54(2):304–310. doi: 10.1128/jvi.54.2.304-310.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vennström B., Fanshier L., Moscovici C., Bishop J. M. Molecular cloning of the avian erythroblastosis virus genome and recovery of oncogenic virus by transfection of chicken cells. J Virol. 1980 Nov;36(2):575–585. doi: 10.1128/jvi.36.2.575-585.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weidner U., Peter S., Strohmeyer T., Hussnätter R., Ackermann R., Sies H. Inverse relationship of epidermal growth factor receptor and HER2/neu gene expression in human renal cell carcinoma. Cancer Res. 1990 Aug 1;50(15):4504–4509. [PubMed] [Google Scholar]
- Yamamoto T., Hihara H., Nishida T., Kawai S., Toyoshima K. A new avian erythroblastosis virus, AEV-H, carries erbB gene responsible for the induction of both erythroblastosis and sarcomas. Cell. 1983 Aug;34(1):225–232. doi: 10.1016/0092-8674(83)90153-8. [DOI] [PubMed] [Google Scholar]
- Yamamoto T., Nishida T., Miyajima N., Kawai S., Ooi T., Toyoshima K. The erbB gene of avian erythroblastosis virus is a member of the src gene family. Cell. 1983 Nov;35(1):71–78. doi: 10.1016/0092-8674(83)90209-x. [DOI] [PubMed] [Google Scholar]
- Yao M., Shuin T., Misaki H., Kubota Y. Enhanced expression of c-myc and epidermal growth factor receptor (C-erbB-1) genes in primary human renal cancer. Cancer Res. 1988 Dec 1;48(23):6753–6757. [PubMed] [Google Scholar]