Post-Transcriptional Regulation of the Abundance of mRNAs ...
Expression of the gastrin-releasing peptide gene in human small cell lung cancer. Evidence for...
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82 Expression of the Gastrin-Releasing Pep- tide Gene in Human Small Cell Lung Cancer. Evidence for Alternative Process- ing Resulting in Three Distinct mRNAs. Sausville, E.A., Lebacq-Verheyden, A.-M., Spindel, E.R. et al. Navy Medical Oncol- ogy Branch, Clinical Oncology Program, National Cancer Institute, National In- stitutes of Health, Bethesda, MD 20814, U.S.A. J. Biol. Chem. 261: 2451-2457, 1986. cDNA clones to human prepro-gastrin- releasing peptide (prepro-GRP) mRNA detect synthesis of prepro-GRP-related transcripts in 4 of 7 small cell lung cancer (SCLC) cell lines and 1 of 2 metastatic SCLC tumor examined. A cor- relation is noted between prepro-GRP gene expression and the occurrqnce of bombesin-related immunoreactJ~,~y in SCLC cell lines. Examination of the structure of prepro-GRP transcripts found in SCLC reveals three types of prepro-GRP mRNA which differ in the structure of a puta- tive GRP-associated peptide in the pro- GRP precursor. The subcellular distribu- tion of prepro-GRP-related RNAs and structure of SCLC-derived prepro-GRP cDNA clones suggest that all three types of transcript could function as mRNAs, al- though there are differences in the prevalence of the different RNA types in different cellular compartments. Com- parison of the sequence of cDNA clones with the sequence of a genomic prepro-GRP clone reveals that the three forms of prepro-GRP mRNA arise from a single primary transcript which undergoes alter- native processing from two splice donor sites to two splice acceptor sites. The predicted amino acid sequence of the translated products of the three mRNAs are quite distinct, leading to predicted pro-GRP molecules of differing structure. Comparison of Characteristics of Human Small Cell Carcinoma of the Lung in Patients, in Vitro and Transplanted Into Nude Mice. Engelholm, S.Aa., Spang-Thomsen, M., Vindel~v, L.L. et al. University In- stitute of Pathological Anatomy, Univer- sity of Copenhagen, Copenhagen, Denmark. Acta. Pathol. MicroDio±. Immunol. Scand. 94: 325-336, 1986. Specimens from 24 patients with metastatic small cell carcinoma of the lung were explanted in vitro as well as transplanted directly into nude mice. A method to obtain fibroblast-free cultures is described. This method resulted in cell lines which could be grown for more than one year in 79% of the cases. Fifty- four % of the tumours could be estab- lished as serially transplantable tumours in nude mice. The tumours were charac- terized by histology, electron microscopy, DNA index, and cell cycle distribution. The in vitro cell lines were furthermore characterized by the plating efficiency and by doubling time. The macroscopic growth of the heterotransplanted tumours was ascribed to a transformed Gompertz function. The tumour cells preserved their light micro- scopic constitution of small cell car- cinoma of the lung in the model systems. The heterogeneity of the original tumours was reflected in vitro and in nude mice and the model systems thus allows an ex- pression of the inherent heterogeneity and instability. The panel of transplant- able tumours and the in vitro cell lines offer the study of biology inclusive of tumour progression of SCCL. Localisation of Lung Cancer by a Radiolabelled Monoclonal Antibody Against the C-Myc Oncogene Product. Chan, S.Y.T., Evan, G.I., Ritson, A. et al. Ludwig Institute for Cancer Research, MRC Centre, Cambridge CB2 2QH, UK. Br. J. Cancer 54: 761-769, 1986. A set of mouse monoclonal antibodies against the c-myc oncogene product, a 62,000 dalton nuclear binding protein in- volved in cell cycle control, has been constructed by immunisation with syn- thetic peptide fragments. One such antibody, CTI4, was radiolabelled with 131I and administered to 20 patients with different malignant diseases. Good tumour localisation was observed in 12 out of 14 patient with primary bronchial carcinoma but not in patients with pulmonary metas- tases from primary tumours elsewhere. Successfully antibodies against oncogene products may provide novel selective tools for the diagnosis and therapy of cancer. Biosynthesis and Expression of the Dis- ialoganglioside G(D2), a relevant Target Antigen on Small Cell Lung Carcinoma for Monoclonal Antibody Cytolysis. Cheresh, D.A., Rosenberg, J., Mujoo, K. et al. Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA, U.S.A. Cancer Res. 46: 5112-5118, 1986. Monoclonal antibodies (MAbs) 126 (immunoglobulin M) and 14.18 (immunoglobulin G3) react strongly with the cell surface of small cell carcinoma of the lungs (SCCL) and are unreactive with most normal tissues and other neoplasms with the notable exception of tumors derived from cells of neural crest origin. These MAbs react specifically with the oligosaccharide portion of the disialoganglioside G(D2). Analysis of to- tal gangliosides from cultured cell lines derived from SCCL indicates that G(D2) is a predominant ganglioside. A comparison of the reactivities of MAbs against G(2D) with those directed against gangliosides G(M2) and G(D3), each differing from G(D2) by a single sugar residue, clearly indicates that G(D2) is preferentially expressed by cultured cells derived from SCCL. Membranes isolated from these cells exhibit G(D2) synthetase activity which
Transcript of Expression of the gastrin-releasing peptide gene in human small cell lung cancer. Evidence for...
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Expression of the Gastrin-Releasing Pep- tide Gene in Human Small Cell Lung Cancer. Evidence for Alternative Process- ing Resulting in Three Distinct mRNAs. Sausville, E.A., Lebacq-Verheyden, A.-M., Spindel, E.R. et al. Navy Medical Oncol- ogy Branch, Clinical Oncology Program, National Cancer Institute, National In- stitutes of Health, Bethesda, MD 20814, U.S.A. J. Biol. Chem. 261: 2451-2457, 1986.
cDNA clones to human prepro-gastrin- releasing peptide (prepro-GRP) mRNA detect synthesis of prepro-GRP-related transcripts in 4 of 7 small cell lung cancer (SCLC) cell lines and 1 of 2 metastatic SCLC tumor examined. A cor- relation is noted between prepro-GRP gene expression and the occurrqnce of bombesin-related immunoreactJ~,~y in SCLC cell lines. Examination of the structure of prepro-GRP transcripts found in SCLC reveals three types of prepro-GRP mRNA which differ in the structure of a puta- tive GRP-associated peptide in the pro- GRP precursor. The subcellular distribu- tion of prepro-GRP-related RNAs and structure of SCLC-derived prepro-GRP cDNA clones suggest that all three types of transcript could function as mRNAs, al- though there are differences in the prevalence of the different RNA types in different cellular compartments. Com- parison of the sequence of cDNA clones with the sequence of a genomic prepro-GRP clone reveals that the three forms of prepro-GRP mRNA arise from a single primary transcript which undergoes alter- native processing from two splice donor sites to two splice acceptor sites. The predicted amino acid sequence of the translated products of the three mRNAs are quite distinct, leading to predicted pro-GRP molecules of differing structure.
Comparison of Characteristics of Human Small Cell Carcinoma of the Lung in Patients, in Vitro and Transplanted Into Nude Mice. Engelholm, S.Aa., Spang-Thomsen, M., Vindel~v, L.L. et al. University In- stitute of Pathological Anatomy, Univer- sity of Copenhagen, Copenhagen, Denmark. Acta. Pathol. MicroDio±. Immunol. Scand. 94: 325-336, 1986.
Specimens from 24 patients with metastatic small cell carcinoma of the lung were explanted in vitro as well as transplanted directly into nude mice. A method to obtain fibroblast-free cultures is described. This method resulted in cell lines which could be grown for more than one year in 79% of the cases. Fifty- four % of the tumours could be estab- lished as serially transplantable tumours in nude mice. The tumours were charac- terized by histology, electron microscopy, DNA index, and cell cycle distribution. The in vitro cell lines were furthermore characterized by the plating efficiency and by doubling time.
The macroscopic growth of the heterotransplanted tumours was ascribed to a transformed Gompertz function. The tumour cells preserved their light micro- scopic constitution of small cell car- cinoma of the lung in the model systems. The heterogeneity of the original tumours was reflected in vitro and in nude mice and the model systems thus allows an ex- pression of the inherent heterogeneity and instability. The panel of transplant- able tumours and the in vitro cell lines offer the study of biology inclusive of tumour progression of SCCL.
Localisation of Lung Cancer by a Radiolabelled Monoclonal Antibody Against the C-Myc Oncogene Product. Chan, S.Y.T., Evan, G.I., Ritson, A. et al. Ludwig Institute for Cancer Research, MRC Centre, Cambridge CB2 2QH, UK. Br. J. Cancer 54: 761-769, 1986.
A set of mouse monoclonal antibodies against the c-myc oncogene product, a 62,000 dalton nuclear binding protein in- volved in cell cycle control, has been constructed by immunisation with syn- thetic peptide fragments. One such antibody, CTI4, was radiolabelled with 131I and administered to 20 patients with different malignant diseases. Good tumour localisation was observed in 12 out of 14 patient with primary bronchial carcinoma but not in patients with pulmonary metas- tases from primary tumours elsewhere. Successfully antibodies against oncogene products may provide novel selective tools for the diagnosis and therapy of cancer.
Biosynthesis and Expression of the Dis- ialoganglioside G(D2), a relevant Target Antigen on Small Cell Lung Carcinoma for Monoclonal Antibody Cytolysis. Cheresh, D.A., Rosenberg, J., Mujoo, K. et al. Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA, U.S.A. Cancer Res. 46: 5112-5118, 1986.
Monoclonal antibodies (MAbs) 126 (immunoglobulin M) and 14.18 (immunoglobulin G3) react strongly with the cell surface of small cell carcinoma of the lungs (SCCL) and are unreactive with most normal tissues and other neoplasms with the notable exception of tumors derived from cells of neural crest origin. These MAbs react specifically with the oligosaccharide portion of the disialoganglioside G(D2). Analysis of to- tal gangliosides from cultured cell lines derived from SCCL indicates that G(D2) is a predominant ganglioside. A comparison of the reactivities of MAbs against G(2D) with those directed against gangliosides G(M2) and G(D3), each differing from G(D2) by a single sugar residue, clearly indicates that G(D2) is preferentially expressed by cultured cells derived from SCCL. Membranes isolated from these cells exhibit G(D2) synthetase activity which
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