Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in metastatic melanoma

Protein tyrosine kinases (PTKs) have been implicated in the development of many common human tumours including melanoma. Previously we isolated PTK gene sequences expressed in normal melanocytes. Here we examined expression of 9 of these genes in cell lines derived from defined stages of melanoma progression, by Northern blotting and in some cases immunoblotting. We also tested cells from 2 animal models of particular stages in progression, as well as uncultured biopsies of metastatic melanoma. The expression of 2 receptor kinase family members found in melanocytes, PTK7/CCK‐4 and SEK/TYRO1, was decreased or lost in advanced melanomas. PTK7 mRNA was found in only 54% of melanoma cell lines and 20% of melanoma biopsies. Similarly, expression was lost in 2 advanced cell lines selected from an early melanoma line that did express PTK7 mRNA. SEK/TYRO1 expression was observed in 75% and 17% of cell lines from primary and metastastic melanomas, respectively. Conversely, mRNA for the non‐receptor kinase PTK6/BRK was not detected in normal melanocytes or primary melanoma lines, but was found in 9% of metastatic melanoma cell lines. Int. J. Cancer 71: 1061‐1065, 1997. © 1997 Wiley‐Liss Inc.

[1]  H. Lee,et al.  Characterization of the human full-length PTK7 cDNA encoding a receptor protein tyrosine kinase-like molecule closely related to chick KLG. , 1996, Journal of biochemistry.

[2]  A. Ullrich,et al.  Colon carcinoma kinase-4 defines a new subclass of the receptor tyrosine kinase family. , 1995, Oncogene.

[3]  L. Cantley,et al.  Recognition and specificity in protein tyrosine kinase-mediated signalling. , 1995, Trends in biochemical sciences.

[4]  M. Herlyn,et al.  Protein B61 as a new growth factor: expression of B61 and up-regulation of its receptor epithelial cell kinase during melanoma progression. , 1995, Cancer research.

[5]  M. Schartl,et al.  Human malignant melanoma. A genetic disease? , 1995, Cancer.

[6]  B. Gusterson,et al.  Expression patterns of the novel receptor-like tyrosine kinase, DDR, in human breast tumours. , 1995, Oncogene.

[7]  M. Herlyn,et al.  Abnormal protein tyrosine kinase gene expression during melanoma progression and metastasis , 1995, International journal of cancer.

[8]  M. Herlyn,et al.  Protein kinases in normal and transformed melanocytes , 1994, Melanoma research.

[9]  B. Gusterson,et al.  Cloning and characterisation of cDNAs encoding a novel non-receptor tyrosine kinase, brk, expressed in human breast tumours. , 1994, Oncogene.

[10]  Yosef Yarden,et al.  B61 is a ligand for the ECK receptor protein-tyrosine kinase , 1994, Nature.

[11]  R. Halaban Signal transduction in normal and malignant melanocytes. , 1994, Pigment cell research.

[12]  T. Hunter,et al.  Receptor protein-tyrosine kinases and their signal transduction pathways. , 1994, Annual review of cell biology.

[13]  R. Spritz,et al.  A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes. , 1993, Oncogene.

[14]  M. Herlyn,et al.  Novel and known protein tyrosine kinases and their abnormal expression in human melanoma. , 1993, The Journal of investigative dermatology.

[15]  M. Sudol,et al.  Elevated expression of protein tyrosine kinase c-Yes, but not c-Src, in human malignant melanoma. , 1993, Oncogene.

[16]  P. Comoglio,et al.  Expression of the c-Met/HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progression. , 1993, British Journal of Cancer.

[17]  R. Perlis,et al.  KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells. , 1993, Oncogene.

[18]  N. Nomura,et al.  Expression of the c-ski proto-oncogene in human melanoma cell lines. , 1993, Melanoma research.

[19]  A. Wilks Protein tyrosine kinase growth factor receptors and their ligands in development, differentiation, and cancer. , 1993, Advances in cancer research.

[20]  O. Myklebost,et al.  Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. , 1992, Cancer research.

[21]  A. Ullrich,et al.  Progression of human cutaneous melanoma is associated with loss of expression of c‐kit proto‐oncogene receptor , 1992, International journal of cancer.

[22]  N. Lassam,et al.  Loss of c-kit expression in cultured melanoma cells. , 1992, Oncogene.

[23]  K. Isobe,et al.  Aberrant melanogenesis and melanocytic tumour development in transgenic mice that carry a metallothionein/ret fusion gene. , 1991, The EMBO journal.

[24]  R. Halaban,et al.  Proliferation and malignant transformation of melanocytes. , 1991, Critical reviews in oncogenesis.

[25]  F. Real,et al.  Phenotypic heterogeneity of melanoma. Relation to the differentiation program of melanoma cells , 1987, The Journal of experimental medicine.

[26]  Wallace H. Clark,et al.  Human malignant melanoma , 1979 .