Differential expression of intermediate filament proteins distinguishes classic from variant...
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findings are of considerable biological and clinical interest.
Differential Expression of Intellnediate Filament Proteins Distinguishes Classic from Variant Small-Cell Lung Cancer Cell Lines. Broers, J.L.V., Carney, D.N., De Ley, L. et al. Department of Pathology, Univer- sity of Nijmegen, 6525 GA Nijmegen, Netherlands. Proc. Natl. Acad. Sci. U.S.A. 82: 4409-4413, 1985.
The expression of intermediate fila- ment proteins in classic and variant-type small-cell lung carcinoma (SCLC) cell lines was studied using immunocytochemi- cal techniques, two-dimensional gel elec- trophoresis and immunoblotting assays. Classic SCLC cell lines contain cytokera- tin proteins but no neurofilaments. In contrast, variant cell lines do not con- tain detectable amounts of cytokeratins but partly express neurofilaments and vimentin. These results explain apparent discrepancies on the intermediate fila- ment content of SCLC described in the recent literature. The application of an- tibodies to fresh biopsy specimens of SCLC may in the future allow the identification of the variant type of cells in clinical SCLC specimens and may have a major im- pact of therapeutic strategy and progno- sis in these patients.
Isolation and Characterization of an Ac- tivated c-H-ras-i Gene from a Squamous- Cell Lung Carcinoma Cell Line. Kagimoto, M., Miyoshi, J., Tashiro, K. et al. First Department of Internal Medicine, Faculty of Medicine, Kyushu Uni- versity, Fukuoka 812, Japan. Int. J. Cancer 35: 809-812, 1985.
We determined a complete nucleotide sequence of an activated form of the c-H-ras-i proto-oncogene cloned from the human cell line (QG56), using the DNA transfection technique and NIH3T3 cells as recipients. This cell line was estab- lished from a squamous-cell lung carci- noma of a Japanese patient, and the ac- tivated gene had 2 nucleotide substitu- tions. One substitution of a thymidine for an adenosine was found at position 1069 of the 2898 nucleotide sequence in a restriction endonuclease (SacI) frag- ment, which corresponds to the second base of the 61st codon of the gene enco- ding P21 protein. This nucleotide repla- cement was assumed to be responsible for the transforming activity. Another sub- stitution of a guanosine for an adeno- sine which was detected at position 746 in the first intron was thought to be a genetic polymorphism unassociated with
the transforming activity. Comparisons
of the various lengths of restricted ~ragmencs sug-
gested that the activity was markedly influenced by certain sequences flanking the c-H-ras-i gene.
The Human Vasopressin Gene is Linked to the 0xyto- cin Gene and is Selectively Expressed in a Cultured Lung Cancer Cell Line. sausville, E., Carney, D., Battey, J. National Cancer Institute, Naval Hospital Bethesda, Bethes- da, MD 20814 U.S.A.J. Biol. Chem. 260: 10236-10241, 1985.
The human genes for prepro-arginine-vasopressin- neurophysin II (prepro-AVP-NPII) and prepro-oxyto- cin-neurophysin I (prepro-OT-NPI) were clone~ from a human genomic library and the nucleotide sequen- ce of both genes was determined. The two genes are si milar in their intron-exon structure, linked toge- ther with 12 kilobases intervening, and transcribed from opposite DNA strands. A human small cell lung cancer cell line, H378, produces significant quan- tities of prepro-AVP-NPII mRNA using a transcrip- tion unit predicted from the genomic DNA sequence. Despite the proximity of the activity transcribed prepro-AVP-NPII gene, transcription of prepro-OT- NPI is not detected in this cell line.
Markedly Decreased Expression of Class I Histo- compatibility Antigens, Protein, and mRNA in H~nan Small-Cell Lung Cancer. Doyle, A., Martin, W.J., Funa, K. et al. NCI-Navy Medical Oncology Branch, Division of Cancer Treat- ment, National Cancer Institute, National Insti- tutes of Health, Bethesda, MD 20814, U.S.A.J. Exp. Med. 161: 1135-1151, 1985.
We have found markedly deficient expression of the class I major histocompatibility antigens HLA-A, B, C and beta-2m on human small-cell lung cancer (SCLC) lines and fresh tumor samples. The deficit of HLA-A, B, C and beta.-2-microglobulin (beta-2m) antigen expression was demonstrated with both radiobinding assays and indirect immuno- fluorescence assays. Immunoprecipitation of meta- bolically labeled cells with antibodies to class I antigens showed most SCLC lines to have synthe- sized almost no betasub 2m and HLA-A, B, C prote- ins. Northern blot analysis, using human HLA-A, B, and beta-2m cDNA probes, showed that almost all SCLC lines tested had markedly decreased amounts of HLA and beta-2m mRNA, but both gene products : could be induced with interferon treatment of SCLC lines. We conclude that human SCLC, in contrast to other lung cancer types, is characterized by great- ly reduced transcription of HLA-A, B, C and beta- 2m genes, which suggests the existence of a mecha- nism for evading the host immune response to the tumor and of an Ela-like product in this type of tumor cell.
Bombesin-Like Peptldes can Function as Autocrine Growth Factors in Human Small-Cell Lung Cancer. cuttitta, F., Carney, D. N., Mulshine, J. et al. National Cancer Institute-Navy Medical Oncology Branch, Division of Cancer Treatment, National Can- cer Institute, Bethesda, MD, U.S.A. Nature 316: