L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer
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254 pressed. Although the subclone GLC-1-M13 was derived from the poorly differentiated GLC-1, it behaved according to the above criteria as a differentiated 'classic' SCLC cell line. When assessed with specific monoclonal anti- bodies the different cell lines appeared to express different subsets of intermediate filament proteins, indicative for different stages and directions of differentiation: 'undifferentiated' (GLC-I and GLC-2); 'neu-- ral tissue related' (GLC-2); 'simple epithe- lium' related (GLC-I-MI3); and a combination of simple and squamous epithelium related (GLC-3). We conclude that GLC-I, GLC-2, and GLC-3 represent dedifferentiated forms of SCLC, related to the recently described 'variant' type of SCLC, whereas the clonal derivative GLC-I-MI3 behaves like a diffe- rentiated 'classic' SCLC cell line. Human-Human Hybridomas Secreting Antibodies Specific to Human Lung Carcinoma. Murakami, H., Hashizume, S., Ohashi, H. et al. Food Science and Technology Institute, Kyushu University, Higashi-ku, Fukuoka 812, Japan. In Vitro 21: 593-596, 1985. Human Namalwa cells were screened in serum-free medium and in 6-thuoguanine, then fused with human lymphocytes from lymph no- des of lung adenocarcinoma cancer patients. Extensive testing using 14 lung cancer cell lines, ii other cancer cell lines and 4 nor- mal fibroblast lines identified monoclonal antibodies produced by 4 hydridoma clones that reacted specifically with lung adeno- carcinoma cells. These monoclonal antibodies also reacted with lung adenocarcinoma tis- sues and not normal tissues or erythrocytes of any blood type. These hydridoma clones grew and stably secreted the antibodies in serum-free medium as well as in serum- containing medium. L-MZc, a New Myc-Related Gene Amplified and Expressed in Homan Small Cell Lung Cancer. Nau, M.M., Brooks, B.J., Battey, J. et al. NCI-Navy Medical Oncology Branch, National Cancer Institute, National Institutes of Health & Naval Hospital, Bethesda, MD 20814, U.S.A. Nature 318: 69-73, 1985. Altered structure and regulation of the c-myc proto-oncogene have been associated with a variety of human tumours and deriva- tive cell lines, including Burkitt's lympho- ma, promyelocytic leukaemia and small cell lung cancer (SCLC). The N-myc gene, first detected by its homology to the second exon of the c-myc gene, is amplified and/or ex- pressed in tumours or cell lines derived from neuroblastoma, retinoblastoma and SCLC. Here we describe a third myc-related gene (L-myc) cloned from SCLC DNA with homology to a small region of both the c-myc and N- myc genes. Human genomic DNA shows and EcoRI restriction fragment length polymorphism (RFLP) of L-myc defined by two alleles (i0.0 - and 1.6-kilobase (kb) EcoRI frag- ments), neither associated dispropertionately with SCLC. Mouse and hamster DNAs exhibit a 12-kb EcoRI L-myc homologue, which indi- cates conservation of the gene in mammals. Gene mapping studies assign L-myc to human chromosome region ip32, a location distinct from that of either c-myc or N-myc but asso- ciated with cytogenetic abnormalities in cer- tain human tumours. This L-myc sequence is amplified 10-20-fold in four SCLC cell line DNAs and in one SCLC tumour specimen taken directly from a patient. Either the 10.0- or 6.6-kb allele can be amplified and in heterozygotes only one of the two alleles was amplified in any SCLC genome. SCLC cell lines with amplified L-myc sequences express L-myc-derived transcripts not seen in SCLC with amplified c-myc or N-myc genes. In ad- dition, some SCLCs without amplification also express L-myc-related transcripts. To- gether, these findings suggest an enlarging role for myc-related genes in human lung cancer and provide evidence for the concept of a myc family of proto-oncogenes. Steroid Receptors in H~nan Lung Cancer. Beattie, C.W., Hansen, N.W., Thomas, P.A. Division of Surgical Oncology, College of Medicine, University of Illinois at Chica- go, Chicago, IL 60612, U.S.A. Cancer Res. 45: 4206-4214, 1985. We have determined that a significant incidence of specific high affinity recep- tors for androgen (AR), estrogen (ER), and glucocorticoid (GR) is present in normal adult human lung and bronchogenic carcino- ma cytosols. In contrast, a limited number of tumor cytosols bound progesterone. Bind- ing characteristics for each class of ste- roid hormones were similar to those repor- ted for other steroid-responsive normal and neoplastic tissue. ER was evenly distribu- ted between squamous cell and adenocarci- noma cytosols with a slightly lower affini- ty, but higher content than normal lung. In normal lung, GR resolved into two distinct binding components based on affinity using a dextran-coated charcoal assay. AR in squa- mous cell carcinomas behaved in a similar manner. This was not observed when hydroxya- patite was used to separate bound from free ligand. When AR affinity and content were stratified on the basis of tumor grade in squamous cell carcinoma, the most undiffe- rentiated tumors had a lower AR content and higher affinity. In contrast, there was no differentiation of AR content or affinity based on tumor grade in adenocarcinoma where AR also did not resolve into two distinct groups based on binding affinity. Although related to tumor grade, AR incidence and content were not related to stage of dis- ease. In adenocarcinoma, initial results suggest GR affinity and content were inver-
Transcript of L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer
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pressed. Although the subclone GLC-1-M13 was derived from the poorly differentiated GLC-1, it behaved according to the above criteria
as a differentiated 'classic' SCLC cell line. When assessed with specific monoclonal anti- bodies the different cell lines appeared to express different subsets of intermediate filament proteins, indicative for different stages and directions of differentiation: 'undifferentiated' (GLC-I and GLC-2); 'neu-- ral tissue related' (GLC-2); 'simple epithe- lium' related (GLC-I-MI3); and a combination of simple and squamous epithelium related (GLC-3). We conclude that GLC-I, GLC-2, and GLC-3 represent dedifferentiated forms of SCLC, related to the recently described 'variant' type of SCLC, whereas the clonal derivative GLC-I-MI3 behaves like a diffe- rentiated 'classic' SCLC cell line.
Human-Human Hybridomas Secreting Antibodies Specific to Human Lung Carcinoma. Murakami, H., Hashizume, S., Ohashi, H. et al. Food Science and Technology Institute, Kyushu University, Higashi-ku, Fukuoka 812, Japan. In Vitro 21: 593-596, 1985.
Human Namalwa cells were screened in serum-free medium and in 6-thuoguanine, then fused with human lymphocytes from lymph no- des of lung adenocarcinoma cancer patients. Extensive testing using 14 lung cancer cell lines, ii other cancer cell lines and 4 nor- mal fibroblast lines identified monoclonal antibodies produced by 4 hydridoma clones that reacted specifically with lung adeno- carcinoma cells. These monoclonal antibodies also reacted with lung adenocarcinoma tis- sues and not normal tissues or erythrocytes of any blood type. These hydridoma clones grew and stably secreted the antibodies in serum-free medium as well as in serum- containing medium.
L-MZc, a New Myc-Related Gene Amplified and Expressed in Homan Small Cell Lung Cancer. Nau, M.M., Brooks, B.J., Battey, J. et al. NCI-Navy Medical Oncology Branch, National Cancer Institute, National Institutes of Health & Naval Hospital, Bethesda, MD 20814, U.S.A. Nature 318: 69-73, 1985.
Altered structure and regulation of the c-myc proto-oncogene have been associated with a variety of human tumours and deriva- tive cell lines, including Burkitt's lympho- ma, promyelocytic leukaemia and small cell lung cancer (SCLC). The N-myc gene, first detected by its homology to the second exon of the c-myc gene, is amplified and/or ex- pressed in tumours or cell lines derived from neuroblastoma, retinoblastoma and SCLC. Here we describe a third myc-related gene (L-myc) cloned from SCLC DNA with homology to a small region of both the c-myc and N- myc genes. Human genomic DNA shows and EcoRI
restriction fragment length polymorphism
(RFLP) of L-myc defined by two alleles (i0.0 - and 1.6-kilobase (kb) EcoRI frag- ments), neither associated dispropertionately
with SCLC. Mouse and hamster DNAs exhibit a 12-kb EcoRI L-myc homologue, which indi- cates conservation of the gene in mammals. Gene mapping studies assign L-myc to human chromosome region ip32, a location distinct from that of either c-myc or N-myc but asso- ciated with cytogenetic abnormalities in cer- tain human tumours. This L-myc sequence is amplified 10-20-fold in four SCLC cell line DNAs and in one SCLC tumour specimen taken directly from a patient. Either the 10.0- or 6.6-kb allele can be amplified and in heterozygotes only one of the two alleles was amplified in any SCLC genome. SCLC cell lines with amplified L-myc sequences express L-myc-derived transcripts not seen in SCLC with amplified c-myc or N-myc genes. In ad- dition, some SCLCs without amplification also express L-myc-related transcripts. To- gether, these findings suggest an enlarging role for myc-related genes in human lung cancer and provide evidence for the concept of a myc family of proto-oncogenes.
Steroid Receptors in H~nan Lung Cancer. Beattie, C.W., Hansen, N.W., Thomas, P.A. Division of Surgical Oncology, College of Medicine, University of Illinois at Chica- go, Chicago, IL 60612, U.S.A. Cancer Res. 45: 4206-4214, 1985.
We have determined that a significant incidence of specific high affinity recep- tors for androgen (AR), estrogen (ER), and glucocorticoid (GR) is present in normal adult human lung and bronchogenic carcino- ma cytosols. In contrast, a limited number of tumor cytosols bound progesterone. Bind- ing characteristics for each class of ste- roid hormones were similar to those repor- ted for other steroid-responsive normal and neoplastic tissue. ER was evenly distribu- ted between squamous cell and adenocarci- noma cytosols with a slightly lower affini- ty, but higher content than normal lung. In normal lung, GR resolved into two distinct binding components based on affinity using a dextran-coated charcoal assay. AR in squa- mous cell carcinomas behaved in a similar manner. This was not observed when hydroxya- patite was used to separate bound from free ligand. When AR affinity and content were stratified on the basis of tumor grade in squamous cell carcinoma, the most undiffe- rentiated tumors had a lower AR content and higher affinity. In contrast, there was no differentiation of AR content or affinity based on tumor grade in adenocarcinoma where AR also did not resolve into two distinct groups based on binding affinity. Although related to tumor grade, AR incidence and content were not related to stage of dis- ease. In adenocarcinoma, initial results suggest GR affinity and content were inver-
