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Increased expression of differentiation markers can accompany laminin-induced attachment of small cell lung cancer cells
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provided hiformation on lifetim tasim nod enmkiog. Redott cmbxatmtions tlraumd in 1.573 msidsnats of the study nrbjects showed a lognormal distribotioo with erithm& end gean&c of 127.7 sod 96.0 Bq m’. re+xtively. Lmtg caocer risks tended to iocreese with estimated radon exposme, reaching a nelative risk of 1.7 (95% CoDfideaceiotervalz 1.0-2.9) in women heving aa avetage radon level exceediog 150 Bq m” (4 pCi L“). Sttxmger rssocietioos were suggeetedinyoongerpers0MMdriskcstimateeappsredtobewithill the same range aa those projected for miners. However, Luther shndies are needed to clarify the level of risk associsted with exposure to rmideotial radon. A colmi study of tobacco me, diet, occupation, and lung cancw mortality Chow W-H, Schumm LM, McLaughlin JK, Bjelke E, Gridley 0, WacholderS&d. N~~~(3utmI~~~e,nrriturr.l30EucutiwBoulrwrd. Rodville, MD 20392. Cancer Causea Control 1992;3:247-54. In 1966, * cohort of white melee aged 35 or over, who were policy-boldcoswith~~~BmthcrhOOdInsuMosSociety(Unitsd States), mmpbzted a mail qoeatiooneire cm tobacco ose, diet, nod demogtaphicchu;rteristics. ~gtbs2Oyeorsoffollowup,219lung aocer deaths occurred. Beeidee the etroog relationship with cigarette smoking, we observed an effect on hmg cancerrisk among cllrralt users ofcigers or pipes whowere ooosmokersofcigaretta (rclativerisk [RR] = 3.5, 95 Fcrcetttcoolidence ioterval [CI] = 1.0-12.6) or who were past/occasiooal users of cigarettes (RR = 2.7. CI = 1.4-5.3). In addition, elevated risks (from 1.5 to 2.6) of lung cancer were. found eomog craftsmeatand Iebomrs, with the higheet risks among subjects who worked in the mining or menuhchtring iodustry. No essocintion between comet (m of 1966) use of beer or hard liquor nod lung cancer we8 observed, elthough pest users were et elevated risk. An inverse association between lung caocer nod intakeof fiuits was observed, end risks of bmg cancer were lower among persaos in the highest dietary intakequintileeof vitamios A cod C. Except for oranges, however. none 0ftheioverseIssoc~tiooswitbfruitsordietaynutrieotshPds~sticlllly significant trends. The tindings from this cohort study add to the evidence of an adverse effect of cigar/pipe smoking and possible protective effect of dietary factors 0~1lung cancer risk.
Basic biology Mutagenesisof the K-ros pMoonwgene in mow lung tenors indtnxd by Nstbyl-Nnitrmowm or n-nitrosodietbylamiw You M, Wang Y. Lineen AM, Gunning WT, Stoner GD, Anderson MW. Dejhxnmenl of Pathology. Medical College of Ohio, TOLL?& OH 43699. Cerciiogwle-sis 1992;13:1583-6. The role of ras gene activation in the developmeat of lung hunors induced by N-ethyl-N-nitrosouru (ENU) ad N-nitro.wdietbylPmine (DEN)wasevalwtedintheA/Jmouse, astraiosusccptibletocbemically induced lung hmmrs. DNAs isolated horn both ENU- aod DENioduced lung tmmrs were screened for activatingmotetions in the K-r-as gene by utilizing the polymense chain reaction @CR) nod direct sequence analysis. Mutations in the K-M gw were detected in 11 of 11 ENU-induced tomma end 23 of 28 DEN-Mucal tumors. In ENUinduced honors, there were threz GC AT treositions in the second base ofcodoo 12,eodsevenATGCtmnsitiooseodooeATTAtmosve~sion in the eeumd base of codon 61. A similar spectrumof K-ms mutetioos was observed in DEN-ioduced lung tmnot’e:five GC AT transitionsnod two GC TA tmmxersions in the seaod bese of cadon 12, and sixteen AT GC transitionsat the second base of cadon 61. Ninety-one percent (3 1134) of the observed mutationsare consistent witb the formation of the promutagenic OQbylthymine and OQbylgupnioe adducts in DNA. Therefore, lung tumorsfrom the A/J mouse inducedby DEN nod ENU could be initiated by the interactionof reactive metebolitee with specific sites in the K-ms geoe. This is the first clear example of activation of the K-x-asgene by ethylatingagents in a rodent lung tumor system.
Abstracts/Lung
Cancer IO (1993) 123-IS0
Jmmttnohao&aiLxlaMlysisofnmz3gmepmdud/NDPkilmse expaLEsiOniltpttb&~P&OCt&MM:LM!kOr~VtdUe HigrshiyrrmM,DoiO,YolroucbiH,K~K,N~S,Te~shi R et PI. Dcpruncnr of lhactc Sur~my,Cen&er for AdvltDimu~. Osaka, Nakamich l-3-3, Higarhinariku. Osaka 537. Br J Cancer 1992;66:5336. Levels of 1~23 gene producthcleoside dipko&ate kinpst (NDP me&tic-potaial in several UlmolJrs,indicating that this calid bee useful tool es e prognostic indicator. Usiog M antibody to NDP kinese, levels of mu23 gene ptuduct/NDP kinasa expression in pulmonery adeoocatcioomewereexamioedi mmooohietochemically.Of88 p&i&s tested, 39 (44%; Group B) showed strong immtmotactivity for NDP ~inmostofePncercdlswi~tbetumMlrtiasua,while49(56%; Group A) containedfew or no NDP kinase+sitive cancer calls. Nm23 gene productlNDP kioese WLSexpirxsed indepaiently of cliicopathological factors, and unexpectedly, oo correletioe of SurviveIrates between both Groups could be denmostmted. Thus, in pulmonuy adeuccacioome levels of em23 gene pmduct/NDP kioese exprsssicm mey lack progntiic value. Inwppsed expression of differentiation markers can accompany Iaminin-induced &achnent of mull all lung amcw 4s Gieccone G, Bmers J, Jensen S, Fridmen RI, Limtoile R, Gez&r AF. Free Uniwrsiry Hospital, DepartmemofOncology. De Boclehan 1117, 1081 HVAmrrerdam. Br J Cancer 1992;66:488-95. We investigeted the ioteraction be4weea human lung cancer cells, laminin, and severe1 differentiatiog agents. When grown cm laminin coeted sub&ate eight out of 11 smell cell lung cancer (SCLC) cell lines exhibited attachmentto laminin and three had exteasive outgrowth of loag nellrite-likepmcesses. Of seven non-smalI cell lung cancer cell lmes,selectedfortheirinvitmanchwage-ia~~epeadentgmwth,~t was observed in only t&e cell lines, end process formationwes far less extensive thanin SCLC cell lines. Among severs1 differentiatingageats, only dcAMP, which alooe induced attachment and some process formation,increasedIsminin-mediatedattachment andprocessformatioo of two SCLC cell lines, NCI-N417 P variantcell line, and NCI-H345, a classic cell line. The expression of severel nwroeodocrine nod neuronal markers w&s investigated in these two SCLC cell lines. 7l1e expressiooofthelightsubuaitofneurotilamentsincreasedioNCI-N417 within 3 to 4 daysof seeding, while NC&H345 exhibited approximately 5 fold increase in expression of the GRP gene end P 3 fold increase expression of the fi-actin gene. The expression of P number of other neuroendccrineand neuronalmarkersdid not change following growth on laminin. The doubling times remainedunchaogediodependeat of the p-ce of and attachmentto laminin while to~isomemse II gene expression levels in NC&N417 cells decreased epproximetely 5 fold when cells were growing al laminin. Aberrations of the p53 tumor soppre&sorgene in hnon-smaU cellclvfirmus0fthellmg Kishimoto Y, Murakami Y. Sbiraishi M, Hay& K, Sekiya T. Oncegene Division, Naional Cancer Ctr. Rewxreh InU., I-l, Twkiji 5-&me, Chuo-ka Toky 104. C!mcer Res 1992;52:4799-4804. Aberrations of tbe ~53 gene in 1I5 surgical specimens of non-small cell~iw~ofthelungwereexnmincdbysingle;straodco~fonnstion polymorphianPnrlysisofpolymerPsec~reactioll~ucts.StructurPl abncrmalitiesoftbep53 genewereobservsdio6ohlmors(52%). i.e., 8 of 14 large cell carcioomes, 24 of 58 aderlocalcinomee. 25 of 37 souemous cell carcinoma. and 3 of 6 adenosuoemous cxucinomas. substitutions,9dslstio~soritrsertionofashortaufl~tidesequence, and 3 two-base SutiiNtions in 57 tumrs. h the other 3 tumors, logs of one of the p53 ellelee was observed, with oo mutation in the other allele. Allelic loss of the ~53 gene was observed in 14 of 43 ioformetive cases (33 %), and io 11 of the 14 cases tlii remainiog allele wes muteted. The aberrationsof the p53 gene were not limited to P particularhistological type or clinical stege. Their high frequency suggests thet they were hvolved io the genesis of ow-small cell cafcioome5 of the lung. The
provided hiformation on lifetim tasim nod enmkiog. Redott cmbxatmtions tlraumd in 1.573 msidsnats of the study nrbjects showed a lognormal distribotioo with erithm& end gean&c of 127.7 sod 96.0 Bq m’. re+xtively. Lmtg caocer risks tended to iocreese with estimated radon exposme, reaching a nelative risk of 1.7 (95% CoDfideaceiotervalz 1.0-2.9) in women heving aa avetage radon level exceediog 150 Bq m” (4 pCi L“). Sttxmger rssocietioos were suggeetedinyoongerpers0MMdriskcstimateeappsredtobewithill the same range aa those projected for miners. However, Luther shndies are needed to clarify the level of risk associsted with exposure to rmideotial radon. A colmi study of tobacco me, diet, occupation, and lung cancw mortality Chow W-H, Schumm LM, McLaughlin JK, Bjelke E, Gridley 0, WacholderS&d. N~~~(3utmI~~~e,nrriturr.l30EucutiwBoulrwrd. Rodville, MD 20392. Cancer Causea Control 1992;3:247-54. In 1966, * cohort of white melee aged 35 or over, who were policy-boldcoswith~~~BmthcrhOOdInsuMosSociety(Unitsd States), mmpbzted a mail qoeatiooneire cm tobacco ose, diet, nod demogtaphicchu;rteristics. ~gtbs2Oyeorsoffollowup,219lung aocer deaths occurred. Beeidee the etroog relationship with cigarette smoking, we observed an effect on hmg cancerrisk among cllrralt users ofcigers or pipes whowere ooosmokersofcigaretta (rclativerisk [RR] = 3.5, 95 Fcrcetttcoolidence ioterval [CI] = 1.0-12.6) or who were past/occasiooal users of cigarettes (RR = 2.7. CI = 1.4-5.3). In addition, elevated risks (from 1.5 to 2.6) of lung cancer were. found eomog craftsmeatand Iebomrs, with the higheet risks among subjects who worked in the mining or menuhchtring iodustry. No essocintion between comet (m of 1966) use of beer or hard liquor nod lung cancer we8 observed, elthough pest users were et elevated risk. An inverse association between lung caocer nod intakeof fiuits was observed, end risks of bmg cancer were lower among persaos in the highest dietary intakequintileeof vitamios A cod C. Except for oranges, however. none 0ftheioverseIssoc~tiooswitbfruitsordietaynutrieotshPds~sticlllly significant trends. The tindings from this cohort study add to the evidence of an adverse effect of cigar/pipe smoking and possible protective effect of dietary factors 0~1lung cancer risk.
Basic biology Mutagenesisof the K-ros pMoonwgene in mow lung tenors indtnxd by Nstbyl-Nnitrmowm or n-nitrosodietbylamiw You M, Wang Y. Lineen AM, Gunning WT, Stoner GD, Anderson MW. Dejhxnmenl of Pathology. Medical College of Ohio, TOLL?& OH 43699. Cerciiogwle-sis 1992;13:1583-6. The role of ras gene activation in the developmeat of lung hunors induced by N-ethyl-N-nitrosouru (ENU) ad N-nitro.wdietbylPmine (DEN)wasevalwtedintheA/Jmouse, astraiosusccptibletocbemically induced lung hmmrs. DNAs isolated horn both ENU- aod DENioduced lung tmmrs were screened for activatingmotetions in the K-r-as gene by utilizing the polymense chain reaction @CR) nod direct sequence analysis. Mutations in the K-M gw were detected in 11 of 11 ENU-induced tomma end 23 of 28 DEN-Mucal tumors. In ENUinduced honors, there were threz GC AT treositions in the second base ofcodoo 12,eodsevenATGCtmnsitiooseodooeATTAtmosve~sion in the eeumd base of codon 61. A similar spectrumof K-ms mutetioos was observed in DEN-ioduced lung tmnot’e:five GC AT transitionsnod two GC TA tmmxersions in the seaod bese of cadon 12, and sixteen AT GC transitionsat the second base of cadon 61. Ninety-one percent (3 1134) of the observed mutationsare consistent witb the formation of the promutagenic OQbylthymine and OQbylgupnioe adducts in DNA. Therefore, lung tumorsfrom the A/J mouse inducedby DEN nod ENU could be initiated by the interactionof reactive metebolitee with specific sites in the K-ms geoe. This is the first clear example of activation of the K-x-asgene by ethylatingagents in a rodent lung tumor system.
Abstracts/Lung
Cancer IO (1993) 123-IS0
Jmmttnohao&aiLxlaMlysisofnmz3gmepmdud/NDPkilmse expaLEsiOniltpttb&~P&OCt&MM:LM!kOr~VtdUe HigrshiyrrmM,DoiO,YolroucbiH,K~K,N~S,Te~shi R et PI. Dcpruncnr of lhactc Sur~my,Cen&er for AdvltDimu~. Osaka, Nakamich l-3-3, Higarhinariku. Osaka 537. Br J Cancer 1992;66:5336. Levels of 1~23 gene producthcleoside dipko&ate kinpst (NDP me&tic-potaial in several UlmolJrs,indicating that this calid bee useful tool es e prognostic indicator. Usiog M antibody to NDP kinese, levels of mu23 gene ptuduct/NDP kinasa expression in pulmonery adeoocatcioomewereexamioedi mmooohietochemically.Of88 p&i&s tested, 39 (44%; Group B) showed strong immtmotactivity for NDP ~inmostofePncercdlswi~tbetumMlrtiasua,while49(56%; Group A) containedfew or no NDP kinase+sitive cancer calls. Nm23 gene productlNDP kioese WLSexpirxsed indepaiently of cliicopathological factors, and unexpectedly, oo correletioe of SurviveIrates between both Groups could be denmostmted. Thus, in pulmonuy adeuccacioome levels of em23 gene pmduct/NDP kioese exprsssicm mey lack progntiic value. Inwppsed expression of differentiation markers can accompany Iaminin-induced &achnent of mull all lung amcw 4s Gieccone G, Bmers J, Jensen S, Fridmen RI, Limtoile R, Gez&r AF. Free Uniwrsiry Hospital, DepartmemofOncology. De Boclehan 1117, 1081 HVAmrrerdam. Br J Cancer 1992;66:488-95. We investigeted the ioteraction be4weea human lung cancer cells, laminin, and severe1 differentiatiog agents. When grown cm laminin coeted sub&ate eight out of 11 smell cell lung cancer (SCLC) cell lines exhibited attachmentto laminin and three had exteasive outgrowth of loag nellrite-likepmcesses. Of seven non-smalI cell lung cancer cell lmes,selectedfortheirinvitmanchwage-ia~~epeadentgmwth,~t was observed in only t&e cell lines, end process formationwes far less extensive thanin SCLC cell lines. Among severs1 differentiatingageats, only dcAMP, which alooe induced attachment and some process formation,increasedIsminin-mediatedattachment andprocessformatioo of two SCLC cell lines, NCI-N417 P variantcell line, and NCI-H345, a classic cell line. The expression of severel nwroeodocrine nod neuronal markers w&s investigated in these two SCLC cell lines. 7l1e expressiooofthelightsubuaitofneurotilamentsincreasedioNCI-N417 within 3 to 4 daysof seeding, while NC&H345 exhibited approximately 5 fold increase in expression of the GRP gene end P 3 fold increase expression of the fi-actin gene. The expression of P number of other neuroendccrineand neuronalmarkersdid not change following growth on laminin. The doubling times remainedunchaogediodependeat of the p-ce of and attachmentto laminin while to~isomemse II gene expression levels in NC&N417 cells decreased epproximetely 5 fold when cells were growing al laminin. Aberrations of the p53 tumor soppre&sorgene in hnon-smaU cellclvfirmus0fthellmg Kishimoto Y, Murakami Y. Sbiraishi M, Hay& K, Sekiya T. Oncegene Division, Naional Cancer Ctr. Rewxreh InU., I-l, Twkiji 5-&me, Chuo-ka Toky 104. C!mcer Res 1992;52:4799-4804. Aberrations of tbe ~53 gene in 1I5 surgical specimens of non-small cell~iw~ofthelungwereexnmincdbysingle;straodco~fonnstion polymorphianPnrlysisofpolymerPsec~reactioll~ucts.StructurPl abncrmalitiesoftbep53 genewereobservsdio6ohlmors(52%). i.e., 8 of 14 large cell carcioomes, 24 of 58 aderlocalcinomee. 25 of 37 souemous cell carcinoma. and 3 of 6 adenosuoemous cxucinomas. substitutions,9dslstio~soritrsertionofashortaufl~tidesequence, and 3 two-base SutiiNtions in 57 tumrs. h the other 3 tumors, logs of one of the p53 ellelee was observed, with oo mutation in the other allele. Allelic loss of the ~53 gene was observed in 14 of 43 ioformetive cases (33 %), and io 11 of the 14 cases tlii remainiog allele wes muteted. The aberrationsof the p53 gene were not limited to P particularhistological type or clinical stege. Their high frequency suggests thet they were hvolved io the genesis of ow-small cell cafcioome5 of the lung. The