A role for the fyn oncogene in metastasis of methylcholanthrene‐induced fibrosarcoma a cells

Expression of various oncogenes (ras, myc, erbB2, src, fyn, yes and sis) in a high‐metastatic clone (MH‐02) derived from a murine methylcholanthrene‐induced fibrosarcoma A (Meth A) was compared with those of its parent clone (ML‐01) by Northern blot analysis. Two oncogenes, fyn, belonging to the tyrosine‐kinase family, and sis, belonging to the cellular‐growth‐factor family, were found to have higher signals (3.6‐fold and 1.8‐fold respectively) in MH‐02 than in ML‐01 cells. To explore the possibility that higher expression of these oncogenes is involved in enhanced metastasis of the MH‐02 clone, ML‐01 was transfected by a fyn vector and the metastatic potential of the transfectant was examined. Mice administered fyn‐transfected ML‐01 cells had significantly increased metastatic nodules in the lung, as compared with those whose ML‐01 cells were transfected with control vector without the fyn gene. The result indicates that the fyn gene is one of the factors governing the metastatic potential of Meth A cells.

[1]  T. Takayama,et al.  Augmented Expression of a Type IV Collagen‐binding Protein in a Highly Metastatic Murine Fibrosarcoma Clone , 1993, Japanese journal of cancer research : Gann.

[2]  M. Hung,et al.  Expression of activated rat neu oncogene is sufficient to induce experimental metastasis in 3T3 cells. , 1991, Oncogene.

[3]  T. Takayama,et al.  Platelet Aggregation Induced by Adenosine Diphosphate Released from Cloned Murine Fibrosarcoma Cells Is Positively Correlated with the Experimental Metastatic Potential of the Cells , 1991, Japanese journal of cancer research : Gann.

[4]  Y. Matsuzawa,et al.  Transformation of chicken embryo fibroblast cells by avian retroviruses containing the human Fyn gene and its mutated genes , 1990, Molecular and cellular biology.

[5]  S. Courtneidge,et al.  Identification and characterization of p59fyn (a src‐like protein tyrosine kinase) in normal and polyoma virus transformed cells. , 1988, The EMBO journal.

[6]  M. J. van de Vijver,et al.  Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. , 1988, The New England journal of medicine.

[7]  L. Eisenbach,et al.  What makes a tumor cell metastatic? , 1988, Scientific American.

[8]  H. Hanafusa,et al.  Phosphorylation of cellular proteins in Rous sarcoma virus-infected cells: analysis by use of anti-phosphotyrosine antibodies , 1988, Molecular and cellular biology.

[9]  M. Radman,et al.  The high fidelity of DNA duplication. , 1988, Scientific American.

[10]  A. Chambers,et al.  Clonal heterogeneity, experimental metastatic ability, and p21 expression in H-ras-transformed NIH 3T3 cells. , 1988, Journal of the National Cancer Institute.

[11]  S. Aaronson,et al.  Acquisition of transforming properties by FYN, a normal SRC-related human gene. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M Terada,et al.  Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[13]  K. Yanagihara,et al.  Transformation by oncogenes encoding protein kinases induces the metastatic phenotype. , 1987, Science.

[14]  J. Costa,et al.  Prognostic implications of expression of the cellular genes myc, fos, Ha‐ras and Ki‐ras in colon carcinoma , 1987, International journal of cancer.

[15]  R. Kerbel,et al.  Alteration of the tumorigenic and metastatic properties of neoplastic cells is associated with the process of calcium phosphate-mediated DNA transfection. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[16]  K. Semba,et al.  Characterization of cDNA clones for the human c-yes gene , 1987, Molecular and cellular biology.

[17]  K. Robbins,et al.  Isolation and oncogenic potential of a novel human src-like gene , 1986, Molecular and cellular biology.

[18]  T. Mitsudomi,et al.  fos oncogene transfer to a transformed rat fibroblast cell line enhances spontaneous lung metastasis in rat. , 1986, Japanese journal of cancer research : Gann.

[19]  M. Yoshida,et al.  yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Storer,et al.  Experimental metastasis in nude mice of NIH 3T3 cells containing various ras genes. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[21]  N. Nomura,et al.  Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor , 1986, Nature.

[22]  R. Kurzrock,et al.  Expression of p21ras in fresh primary and metastatic human colorectal tumors. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[23]  L. Liotta,et al.  NIH/3T3 cells transfected with human tumor DNA containing activated ras oncogenes express the metastatic phenotype in nude mice , 1985, Molecular and cellular biology.

[24]  S. Hirohashi,et al.  A novel combination of K‐ras and myc amplification accompanied by point mutational activation of K‐ras in a human lung cancer. , 1984, The EMBO journal.

[25]  P. Hand,et al.  Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases , 1984, Nature.

[26]  R F Doolittle,et al.  Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. , 1983, Science.

[27]  W. Gilbert,et al.  Nucleotide sequence of rous sarcoma virus , 1983, Cell.

[28]  E. Reddy,et al.  Nucleotide sequence of the simian sarcoma virus genome: demonstration that its acquired cellular sequences encode the transforming gene product p28sis. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[29]  M. Martin,et al.  Organization and stability of endogenous xenotropic murine leukemia virus proviral DNA in mouse genomes , 1983, Journal of virology.

[30]  J. Maizel,et al.  Nucleotide sequence of the p21 transforming protein of Harvey murine sarcoma virus. , 1982, Science.

[31]  R. Mulligan,et al.  Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumour virus chimaeric plasmids , 1981, Nature.

[32]  H. Varmus,et al.  Molecular cloning and characterization of avian sarcoma virus circular DNA molecules , 1980, Journal of virology.

[33]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[34]  I. Fidler,et al.  Selection of successive tumour lines for metastasis. , 1973, Nature: New biology.

[35]  N. Yuhki,et al.  Metastatic ability and expression of c-fos oncogene in cell clones of a spontaneous rat mammary tumor. , 1986, Japanese journal of cancer research : Gann.

[36]  C. Yanisch-Perron,et al.  Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. , 1985, Gene.