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Small cell lung carcinoma cell lines express mRNA for calcitonin and alpha- and beta-calcitonin gene related peptides
Abstracts/Lung
Cancer
Asbestos exposure and smoking habits have been taken into account. The calculated pooled relative risk estimate was 1.94 with a 95% confidence interval of 1.28-2.93. This result suggests a causal relation between exposure to stainless steel welding and lung cancer.
Contemporary situation of screening and primary prevention in contml of lung cancer Kubii A. Mitvvicka 1096. 182 00 Praha 8. Stud Pneumol Phtiseol 1994;54: 123-30. Roentgen-ray or cytologic screening in the case of lung cancer was not successiid and in none of the long-term studies decreased the mortality on lung cancer. Therefore it is not recommended for health service. The basic approach to decrease the incidence of lung cancer is primary prevention. Among the primary preventive measures the most important is the complex control of smoking according to the World Health Organization and International Union Against Cancer.
Exposure and disposition in the development of lung cancer Rudiger Hw. Klinische Abteilung Arbeitsmedizin, Univ. -Klinik fir Innem Medizin /V U&e&tat wien, Wohriager Gurtel 18-20, A-1090 Wien. Atemwegs-Lungekr 1994;ZO:Suppl l:S37-S40. Many environmental and occupational carcinogens may lead to the development of lung cancer in man. Beside the carcinogen exposure, however, there is evidence that also a genetic pm&position may increase the individual risk for these neoplasms. The latter is based in general on an enhanced sensitivity to the cancerogenic attack, either due to an impaired mucociliary clearance, an altered metabolic activation, or inactivation of procarcinogens, or a reduced DNA-repair. These mechanisms are illustrated by experimental data.
Basic biology Molecular anaIysis of the HUD gee encoding a paraneoplastic eacephalomyelitis antigen in human lung cancer cell lines Sekido Y, Bader SA, Carbone DP, Johnson BE, Mimta JD. Simmons Cancer Centec Texas University SWMedical Centec 5323 Harry Hines Boulevard, Dallas, TX 75235-8590. Cancer Res 1994;54:4988-92. Small cell lung cancer (SCLC) is known to express the HUD protein, the neuronal antigen homologous to Drosophila Elav and Sxl genes involved in neuronal and sex development. HUD is the target of an immune response including high titered antibodies causing paraneoplastic encephalomyelitis and sensory neuropathy. Because the ~53 recessive oncogene is mutated and anti-p53 antibodies frequently occur in cancer patients, we wondered if the development of anti-HUD antibodies signaled the presence of HUD mutations in long cancer. The HuD gene was mapped to chromosome region lp using a human- mouse hybrid cell panel. We confirmed that 26 of 46 cancer (43 lung cancer and 3 mesothelioma) cell lines expressed HuD mRNA and that this expression, as well as protein expression by Western blot, correlated strongly with the SCLC neuroendocrine phenotype. Southern blot and single-strand conformation polymorphism analyses showed that HuD was not mutated in 78 lung cancers, including patients with the severe paraneoplastic syndrome. Northern blot analysis showed that lung cancer cell lines expressed two major mRNAs (4.3 and 4.0 kilobases) of HUD. We found the three previously described alternative spliced mRNA forms (HuDpro, HuD, and HuDmex). In addition we also found HuD mRNA had an alternative splicing form in its 5’-coding region. This alternative splice introduced 87 base pairs of sequence and a termination codon
I2 (1995)
113-160
119
resulting in a predicted small, truncated protein (11 amino acids) reminiscent of the male-specific truncated protein in the Sex-lethal (Sxl) gene of Drosophila. However, mRNAs encoding both full-length and truncated proteins were expressed in all SCLCs. These results show that the HuD gene is not mutated in lung cancer, including tumors from patients producing anti-HuD antibodies, but HuD expression is an independent marker or determinant of the neuroendocrine differentiation seen in SCLC.
Small cell lung carcinoma cell lines express mRNA for calcitonin and alpha- and beta-calcitonin gene related peptides Kelley MJ, Snider RH, Becker KL,, Johnson BE. National Cancer Institute, Nay Medical Oncology Branch, Bethesda, MD 20889. Cancer Lett 1994;81:19-25. Calcitonin (CT) and calcitonin gene related peptide (CGRP) are derived from preprohormones encoded by three mRNAs (CT, a-CGRP and DCGRP) from two genes (CALCL and CALCZ) on chromosome 11. Among 16 small cell lung cancer cell lines examined by RNase protection assay, 9 (56%) had detectable CT mRNA, 8 (50%) had aCGRP mRNA, and 13 (81%) had 5-CGRP mRNA. At least one CALCl transcript (CT or a-CGRP) was found in 11 (69%) cell lines with three having only CT mRNA, two having only a-CGRP mRNA, and six having both. a-CGRP mRNA was detected in all of these 11 cell lines expressing a CALC 1 transcript. Immunoreactive CT was detected by radioimmunoassay in eight of nine SCLC cell lines expressing CT mRNA, and immunoreactive CGRP was detected in 12 of 13 cell lines expressing a CGRP mRNA. The variety of expression of these three peptides in different cell lines of the same cell type should provide a useful system for further study of the control of expression of these peptides.
Integrin expression and ability to adhere to extracellular matrix proteins aad endothelial cells in humaa lung caacer lines HirasawaM, Shijubo N, Uede T, Abe S. ThittIDepf o/lnternatMedidne, Sappon, Medical Universily, School of Medicine, Chuo-ku, Sappom 060. Br J Cancer 1994;70:466-73. We examined the integrin expression in 19 hmnan lung cancer cell lines with moncclonal antibodies to the integrin subunits a,, a,, a,, a,, ap a6, 5,. 5,, and 5,. We meanned their ability to adhere to the extmcelhdar matrix (ECM) and human umbilical vein endothelial cells (HUVBCs). Almost all lines expressed the 5, subunit and approximately halfof the Subunits a2, a,, a, and as were frequency expressed, whereas‘very few lines expressed a, and c,,. Most lines adhered strongly to ECM (type I collagen, huninin and ftbroncctin) in correspondence to their expression of integrins. Binding by most lines to tibronectin was completely inhibited by arginine-glycine-aspartic acid (RGD) peptide. Three lines that expressed few or no integrins bad very weak ability to adhere to ECM. Strong binding to HUVECs was found in most lines, but the three lines had very little ability to adhere to HUVECs. Binding to HUVBCs was strongly inhibited at 4”C, under divalent cation-free conditions and by antibodies to the 5, subunit. These results suggest that lung cancer cells adhere to ECM and endothelial cells through integrins, especially the 5, snbfamity.
Cancer
Asbestos exposure and smoking habits have been taken into account. The calculated pooled relative risk estimate was 1.94 with a 95% confidence interval of 1.28-2.93. This result suggests a causal relation between exposure to stainless steel welding and lung cancer.
Contemporary situation of screening and primary prevention in contml of lung cancer Kubii A. Mitvvicka 1096. 182 00 Praha 8. Stud Pneumol Phtiseol 1994;54: 123-30. Roentgen-ray or cytologic screening in the case of lung cancer was not successiid and in none of the long-term studies decreased the mortality on lung cancer. Therefore it is not recommended for health service. The basic approach to decrease the incidence of lung cancer is primary prevention. Among the primary preventive measures the most important is the complex control of smoking according to the World Health Organization and International Union Against Cancer.
Exposure and disposition in the development of lung cancer Rudiger Hw. Klinische Abteilung Arbeitsmedizin, Univ. -Klinik fir Innem Medizin /V U&e&tat wien, Wohriager Gurtel 18-20, A-1090 Wien. Atemwegs-Lungekr 1994;ZO:Suppl l:S37-S40. Many environmental and occupational carcinogens may lead to the development of lung cancer in man. Beside the carcinogen exposure, however, there is evidence that also a genetic pm&position may increase the individual risk for these neoplasms. The latter is based in general on an enhanced sensitivity to the cancerogenic attack, either due to an impaired mucociliary clearance, an altered metabolic activation, or inactivation of procarcinogens, or a reduced DNA-repair. These mechanisms are illustrated by experimental data.
Basic biology Molecular anaIysis of the HUD gee encoding a paraneoplastic eacephalomyelitis antigen in human lung cancer cell lines Sekido Y, Bader SA, Carbone DP, Johnson BE, Mimta JD. Simmons Cancer Centec Texas University SWMedical Centec 5323 Harry Hines Boulevard, Dallas, TX 75235-8590. Cancer Res 1994;54:4988-92. Small cell lung cancer (SCLC) is known to express the HUD protein, the neuronal antigen homologous to Drosophila Elav and Sxl genes involved in neuronal and sex development. HUD is the target of an immune response including high titered antibodies causing paraneoplastic encephalomyelitis and sensory neuropathy. Because the ~53 recessive oncogene is mutated and anti-p53 antibodies frequently occur in cancer patients, we wondered if the development of anti-HUD antibodies signaled the presence of HUD mutations in long cancer. The HuD gene was mapped to chromosome region lp using a human- mouse hybrid cell panel. We confirmed that 26 of 46 cancer (43 lung cancer and 3 mesothelioma) cell lines expressed HuD mRNA and that this expression, as well as protein expression by Western blot, correlated strongly with the SCLC neuroendocrine phenotype. Southern blot and single-strand conformation polymorphism analyses showed that HuD was not mutated in 78 lung cancers, including patients with the severe paraneoplastic syndrome. Northern blot analysis showed that lung cancer cell lines expressed two major mRNAs (4.3 and 4.0 kilobases) of HUD. We found the three previously described alternative spliced mRNA forms (HuDpro, HuD, and HuDmex). In addition we also found HuD mRNA had an alternative splicing form in its 5’-coding region. This alternative splice introduced 87 base pairs of sequence and a termination codon
I2 (1995)
113-160
119
resulting in a predicted small, truncated protein (11 amino acids) reminiscent of the male-specific truncated protein in the Sex-lethal (Sxl) gene of Drosophila. However, mRNAs encoding both full-length and truncated proteins were expressed in all SCLCs. These results show that the HuD gene is not mutated in lung cancer, including tumors from patients producing anti-HuD antibodies, but HuD expression is an independent marker or determinant of the neuroendocrine differentiation seen in SCLC.
Small cell lung carcinoma cell lines express mRNA for calcitonin and alpha- and beta-calcitonin gene related peptides Kelley MJ, Snider RH, Becker KL,, Johnson BE. National Cancer Institute, Nay Medical Oncology Branch, Bethesda, MD 20889. Cancer Lett 1994;81:19-25. Calcitonin (CT) and calcitonin gene related peptide (CGRP) are derived from preprohormones encoded by three mRNAs (CT, a-CGRP and DCGRP) from two genes (CALCL and CALCZ) on chromosome 11. Among 16 small cell lung cancer cell lines examined by RNase protection assay, 9 (56%) had detectable CT mRNA, 8 (50%) had aCGRP mRNA, and 13 (81%) had 5-CGRP mRNA. At least one CALCl transcript (CT or a-CGRP) was found in 11 (69%) cell lines with three having only CT mRNA, two having only a-CGRP mRNA, and six having both. a-CGRP mRNA was detected in all of these 11 cell lines expressing a CALC 1 transcript. Immunoreactive CT was detected by radioimmunoassay in eight of nine SCLC cell lines expressing CT mRNA, and immunoreactive CGRP was detected in 12 of 13 cell lines expressing a CGRP mRNA. The variety of expression of these three peptides in different cell lines of the same cell type should provide a useful system for further study of the control of expression of these peptides.
Integrin expression and ability to adhere to extracellular matrix proteins aad endothelial cells in humaa lung caacer lines HirasawaM, Shijubo N, Uede T, Abe S. ThittIDepf o/lnternatMedidne, Sappon, Medical Universily, School of Medicine, Chuo-ku, Sappom 060. Br J Cancer 1994;70:466-73. We examined the integrin expression in 19 hmnan lung cancer cell lines with moncclonal antibodies to the integrin subunits a,, a,, a,, a,, ap a6, 5,. 5,, and 5,. We meanned their ability to adhere to the extmcelhdar matrix (ECM) and human umbilical vein endothelial cells (HUVBCs). Almost all lines expressed the 5, subunit and approximately halfof the Subunits a2, a,, a, and as were frequency expressed, whereas‘very few lines expressed a, and c,,. Most lines adhered strongly to ECM (type I collagen, huninin and ftbroncctin) in correspondence to their expression of integrins. Binding by most lines to tibronectin was completely inhibited by arginine-glycine-aspartic acid (RGD) peptide. Three lines that expressed few or no integrins bad very weak ability to adhere to ECM. Strong binding to HUVECs was found in most lines, but the three lines had very little ability to adhere to HUVECs. Binding to HUVBCs was strongly inhibited at 4”C, under divalent cation-free conditions and by antibodies to the 5, subunit. These results suggest that lung cancer cells adhere to ECM and endothelial cells through integrins, especially the 5, snbfamity.