Melanoma formation in xiphophorus: A model system for the role of receptor tyrosine kinases in tumorigenesis

Cancer is one of the most frequent fatal human diseases. It is a genetic disease, and molecular analysis of the genes involved revealed that they belong to several distinct classes of molecules, one of which is the receptor tyrosine kinases. Neoplastic transformation is regarded as the result of a multistep process and, in most cases, it is hard to evaluate what the initial events in tumor formation are. What makes it difficult to approach this question is the paucity of animal models for tumorigenesis allowing investigation of the mechanisms leading to uncontrolled cell proliferation. Melanoma formation in Xiphophorus is one of these model systems. Here, overexpression and activation of a receptor tyrosine kinase causes neoplastic transformation of pigment cells. Xiphophorus provides all the advantages of a well‐characterised genetic system. In addition, some crucial components of the transformation pathway have been identified at the molecular level. As a vertebrate, Xiphophorus might serve as a model system to aid understanding, in more general terms, of the mechanisms of tumorigenesis in human diseases.

[1]  K. Semba,et al.  A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[2]  P. Seeburg,et al.  Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells , 1984, Nature.

[3]  Joseph Schlessinger,et al.  Signal transduction by receptors with tyrosine kinase activity , 1990, Cell.

[4]  M. Gordon,et al.  The Genetics of a Viviparous Top-Minnow Platypoecilus; the Inheritance of Two Kinds of Melanophores. , 1927, Genetics.

[5]  M. Schartl,et al.  Autocrine stimulation of the Xmrk receptor tyrosine kinase in Xiphophorus melanoma cells and identification of a source for the physiological ligand. , 1994, The Journal of biological chemistry.

[6]  P. Humphrey,et al.  Structural alterations of the epidermal growth factor receptor gene in human gliomas. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[7]  M. Schartl,et al.  Association between the melanoma-inducing receptor tyrosine kinase Xmrk and src family tyrosine kinases in Xiphophorus. , 1995, Oncogene.

[8]  A. Ullrich,et al.  Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells , 1987, Cell.

[9]  K. Asano,et al.  Gene amplification and overexpression of EGF receptor in squamous cell carcinomas of the head and neck. , 1989, British Journal of Cancer.

[10]  C. James,et al.  Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Schartl,et al.  Elevated expression of the cellular SRC gene in tumors of differing etiologies in xiphophorus , 1985, International journal of cancer.

[12]  M. Ahuja,et al.  A genetic concept of the origin of cancer, based in part upon studies of neoplasms in fishes. , 1976, Progress in experimental tumor research.

[13]  M. Schartl,et al.  Novel putative receptor tyrosine kinase encoded by the melanoma-inducing Tu locus in Xiphophorus , 1989, Nature.

[14]  M. Schartl,et al.  The Xmrk receptor tyrosine kinase is activated in Xiphophorus malignant melanoma. , 1992, The EMBO journal.

[15]  M. Schartl,et al.  Tumor suppression in Xiphophorus by an accidentally acquired promoter. , 1993, Science.

[16]  K. Helin,et al.  The retinoblastoma protein as a transcriptional repressor. , 1993, Trends in cell biology.

[17]  M. Schartl,et al.  Transcriptional activation of the melanoma inducing Xmrk oncogene in Xiphophorus. , 1991, Oncogene.

[18]  M. Schartl,et al.  Correlations of inheritance and expression between a tumor gene and the cellular homolog of the Rous sarcoma virus-transforming gene in Xiphophorus. , 1982, Cancer research.

[19]  M. Schartl,et al.  Xiphophorus as an in vivo model for studies on normal and defective control of oncogenes. , 1984, Advances in cancer research.

[20]  M. Schartl,et al.  Different expression patterns of oncogenes and proto‐oncogenes in hereditary and carcinogen‐induced tumors of xiphophorus , 1993, International journal of cancer.

[21]  M. Schartl,et al.  Identification of a fish protein associated with a kinase activity and related to the Rous sarcoma virus transforming protein. , 1982, Cancer research.

[22]  K. Semba.  A v-erbB-related protooncogene, c-erb-B-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma , 1985 .

[23]  M. Schartl.  A sex chromosomal restriction-fragment-length marker linked to melanoma-determining Tu loci in Xiphophorus. , 1988, Genetics.

[24]  I. Pastan,et al.  Epidermal-growth-factor-dependent transformation by a human EGF receptor proto-oncogene. , 1987, Science.

[25]  F. Anders,et al.  Regulation of Gene Expression in the Gordon-Kosswig Melanoma System , 1973 .

[26]  al. et,et al.  Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B , 1995, Science.

[27]  V. P. Collins,et al.  Functional characterization of an EGF receptor with a truncated extracellular domain expressed in glioblastomas with EGFR gene amplification. , 1994, Oncogene.

[28]  M. Schartl,et al.  RFLP for an EGF-receptor related gene associated with the melanoma oncogene locus of Xiphophorus maculatus. , 1988, Nucleic acids research.

[29]  M. Schartl,et al.  Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene. , 1994, Oncogene.

[30]  B. Woolcock,et al.  Differences in transcription and promoters of Xmrk-1 and Xmrk-2 genes suggest a role for Xmrk-2 in pigment pattern development in the platyfish, Xiphophorus maculatus. , 1994, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[31]  Tony Pawson,et al.  Protein modules and signalling networks , 1995, Nature.

[32]  B. Shilo.  Roles of receptor tyrosine kinases in Drosophila development , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  Cori Bargmann,et al.  Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185 , 1986, Cell.

[34]  M. Schartl,et al.  Spontaneous melanoma formation in nonhybrid Xiphophorus. , 1995, Cancer research.

[35]  W. McGuire,et al.  Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. , 1987, Science.

[36]  D. Baltimore,et al.  Signalling through SH2 and SH3 domains. , 1993, Trends in cell biology.

[37]  T. Hunter,et al.  Protein kinases and phosphatases: The Yin and Yang of protein phosphorylation and signaling , 1995, Cell.

[38]  T Pawson,et al.  SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. , 1991, Science.

[39]  C. Norman.  A Close-Up Look at a Secret Soviet Radar: A visit by a congressional delegation to the infamous Krasnoyarsk radar indicates it would have little value in an ABM system, but probably violates the ABM treaty. , 1987, Science.

[40]  F. Anders,et al.  v-erbB related sequences in Xiphophorus that map to melanoma determining Mendelian loci and overexpress in a melanoma cell line. , 1988, Oncogene.