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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1991 Jul;82(7):820–828. doi: 10.1111/j.1349-7006.1991.tb02708.x

Relation between Nucleolar Size and Growth Characteristics in Small Cell Lung Cancer Cell Lines

Takeo Matsumoto 1,†, Takeo Terasaki 1,✉, Kiyoshi Mukai 1, Makio Wada 2, Aikou Okamoto 2, Jun Yokota 2, Ken Yamaguchi 3, Kanefusa Kato 4, Toshiharu Nagatsu 5, Yukio Shimosato 6
PMCID: PMC5918535  PMID: 1715338

Abstract

Relationships among cytological features, doubling time, S‐phase percentage, expression of myc‐family oncogenes, DNA ploidy and biochemical properties were studied in thirteen small cell lung cancer cell lines. Six cell lines that grew slowly (average doubling time 99 h) and had lower S‐phase percentages (average 32%) showed inconspicuous nncleoli (average area of 1.5 μm2), and the remaining seven cell lines that grew quickly (average doubling time 45 h) and had higher S‐phase percentages (average 44%) showed large and prominent nncleoli (average area of 6.1 μm2). DNA index value obtained from flow cytometric DNA histograms showed that all cell lines except for H‐69 cell line displayed aneuploidy. Ribbon‐like cell arrangements were observed in the 7 cell lines that grew quickly, and in 1 cell line that grew slowly. Biochemically, six slow‐growing cell lines and four fast‐growing cell lines showed high levels of aromatic L‐amino acid decarboxylase activity, while in the remaining three fast‐growing cell lines its level was low. A high level of c‐myc or N‐myc oncogene expression was observed in all 7 cell lines that grew quickly, but not in any of the 6 cell lines that grew slowly. It appears that small cell lung cancer cell lines that grow quickly can be expected to have large nucleoli and ribbon‐like cell arrangements and to express high levels of mycfamily oncogenes, and that nucleolar size is a good indicator for growth characteristics.

Keywords: Morphology, Cell growth, myconcogene family, Small cell lung cancer, in vitro

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REFERENCES

  • 1. ) Shimosato , Y. , Nakajima , T. , Hirohashi , S. , Morinaga , S. , Terasaki , T. , Yamaguchi , K. , Saijo , N. and Suemasu , K.Biological, pathological and clinical features of small cell lung cancer . Cancer Lett. , 33 , 241 – 258 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Vincent , R. G. , Pickren , J. W. , Lane , W. W. , Bross , L. , Takita , H. , Houten , L. , Gutierrez , A. C. and Rzepka , T.The changing histopathology of lung cancer: a review of 1,682 cases . Cancer , 39 , 1647 – 1655 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Yoshimura , K. and Yamashita , N.Clinical statistical observation of 4,931 cases with lung cancer by histological types; results of field study in Japan . Lung Cancer , 22 , 1 – 17 ( 1982. ) ( in Japanese ). [Google Scholar]
  • 4. ) Carney , D. N. , Gazdar , A. F. , Bepler , G. , Guccion , J. G. , Marangos , P. J. , Moody , T. W. , Zweig , M. H. and Minna , J. D.Establishment and identification of small cell lung cancer cell lines having classic and variant features . Cancer Res. , 45 , 2913 – 2923 ( 1985. ). [PubMed] [Google Scholar]
  • 5. ) de Leij , L. , Postmus , P. E. , Buys , C. H. C. M. , Elema , J. D. , Ramaekers , F. , Poppema , S. , Brouwer , M. , van der Veen , A. Y. , Mesander , G. and The , T. H.Characterization of three new variant type cell lines derived from small cell carcinoma of the lung . Cancer Res. , 45 , 6024 – 6033 ( 1985. ). [PubMed] [Google Scholar]
  • 6. ) Sorenson , G. D. , Pettengill , O. S. , Brinck‐Johnsen , T. , Cate , C. C. and Maurer , L. H.Hormone production by cultures of small‐cell carcinoma of the lung . Cancer , 47 , 1289 – 1296 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Gazdar , A. F. , Carney , D. N. , Nau , M. M. and Minna , J. D.Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties . Cancer Res. , 45 , 2924 – 2930 ( 1985. ). [PubMed] [Google Scholar]
  • 8. ) Kiefer , P. E. , Bepler , G. , Kubasch , M. and Havemann , K.Amplification and expression of protooncogenes in human small cell lung cancer cell lines . Cancer Res. , 47 , 6236 – 6242 ( 1987. ). [PubMed] [Google Scholar]
  • 9. ) Takahashi , T. , Obata , Y. , Sekido , Y. , Hida , T. , Ueda , R. , Watanabe , H. , Ariyoshi , Y. , Sugiura , T. and Takahashi , T.Expression and amplification of myc gene family in small cell lung cancer and its relation to biological characteristics . Cancer Res. , 49 , 2683 – 2688 ( 1989. ). [PubMed] [Google Scholar]
  • 10. ) Terasaki , T. , Shimosato , Y. , Nakajima , T. , Tsumuraya , M. , Morinaga , S. , Hirohashi , S. , Yamaguchi , K. , Kato , K. , Ichinose , H. and Nagatsu , T.Changes in cell characteristics due to culture conditions in cell lines from human small cell lung cancer . Jpn. J. Clin. Oncol. , 16 , 203 – 212 ( 1986. ). [PubMed] [Google Scholar]
  • 11. ) Oyama , V. I. and Eagle , H.Measurement of cell growth in tissue culture with a phenol reagent (Folin‐Ciocalteau) . Proc. Soc. Exp. Biol. Med. , 91 , 305 – 307 ( 1956. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Meyer , J. S. , and Coplin , M. D.Thymidine labeling index, flow cytometric S‐phase measurement, and DNA index in human tumors . Am. J. Clin. Pathol. , 89 , 586 – 595 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Bunn , P. A. , Whang‐Peng , J. , Carney , D. N. , Schlam , M. L. , Knutsen , T. and Gazdar , A. F.DNA content analysis by flow cytometry and cytogenetic analysis in mycosis fungoides and Sezary syndrome . J. Clin. Invest. , 65 , 1440 – 1448 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Yokota , J. , Wada , M. , Yoshida , T. , Noguchi , M. , Terasaki , T. , Shimosato , Y. , Sugimura , T. and Terada , M.Heterogeneity of lung cancer cells with respect to the amplification and rearrangement of myc family oncogenes . Oncogens , 2 , 607 – 611 ( 1988. ). [PubMed] [Google Scholar]
  • 15. ) Cleveland , D. W. , Lopata , M. A. , MacDonald , R. J. , Cowan , N. J. , Rutter , W. J. and Kirshner , M. W.Number and evolutionary conservation of α and β‐tubulin and cytoplasmic β and γ‐actin genes using specific cloned cDNA probes . Cell , 20 , 95 – 105 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Nagatsu , T. , Yamamoto , T. and Kato , T.A new and highly sensitive voltametric assay for aromatic L‐amino acid decarboxylase activity by high‐performance liquid chromatography . Anal. Biochem. , 100 , 160 – 165 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Marangos , P. J. , Zis , A. P. , Clark , R. L. and Goodwin , F. K.Neuronal, non‐neuronal and hybrid forms of eno‐lase in brain: structural, immunological and functional comparisons . Brain Res. , 150 , 117 – 133 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Kato , K. , Shimizu , A. , Ishiguro , Y. , Mokuno , K. , Ariyoshi , Y. and Nakajima , T.Highly sensitive enzyme immunoassay for human creatine kinase BB isozyme . Clin. Chim. Acta , 150 , 31 – 40 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Yamaguchi , K‐ , Abe , K. , Kameya , T. , Adachi , I. , Taguchi , S. , Otsubo , K. and Yanaihara , N.Production and molecular size heterogeneity of immunoreactive gastrin‐releasing peptide in fetal and adult lungs and primary lung tumors . Cancer Res. , 43 , 3932 – 3939 ( 1983. ). [PubMed] [Google Scholar]
  • 20. ) Moran , R. , Darzynkiewicz , Z. , Staiano‐coico , L. and Melamed , M. R.Detection of 5‐bromodeoxyuridine (BrdUrd) incorporation by monoclonal antibodies: role of the DNA denaturation step . J Histochem. Cytochem. , 33 , 821 – 827 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Carney , D. N. , Bunn , P. A. , Gazdar , A. F. , Pagan , J. A. and Minna , J. D.Selective growth in serum‐free hormone‐supplemented medium of tumor cells obtained by biopsy from patients with small cell carcinoma of the lung . Proc. Natl. Acad. Sci. USA , 78 , 3185 – 3189 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. ) Waters , J. J. , Ibson , J. M. , Twentyman , P. R. , Bleehen , N. M. and Rabbitts , P. H.Cytogenetic abnormalities in human small cell lung carcinoma: cell lines characterized for myc gene amplification . Cancer Genet. Cytogenet. , 30 , 213 – 223 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Little , C. D. , Nau , M. M. , Carney , D. N. , Gazdar , A. F. and Minna , J. D.Amplification and expression of the c‐myc oncogene in human lung cancer cell lines . Nature , 306 , 194 – 196 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Nau , M. M. , Brooks , B. J. , Carney , D. N. , Gazdar , A. F. , Battey , J. F. , Sausville , E. A. and Minna , J. D.Human small‐cell lung cancers show amplification and expression of the N‐myc gene . Proc. Natl. Acad, Sci. USA , 83 , 1092 – 1096 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Bepler , G. , Jaques , G. , Havemann , K. , Koehler , A. , Johnson , B. E. and Gazdar , A. F.Characterization of two cell lines with distinct phenotypes established from a patient with small cell lung cancer . Cancer Res. , 47 , 1883 – 1891 ( 1987. ). [PubMed] [Google Scholar]
  • 26. ) Johnson , B. E. , Battey , J. , Linnoila , I. , Becker , K. L. , Makuch , R. W. , Snider , R. H. , Carney , D. N. and Minna , J. D.Changes in the phenotype of human small cell lung cancer cell lines after transfection and expression of the c‐myc proto‐oncogene . J Clin. Invest. , 78 , 525 – 532 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. ) Gemma , A. , Nakajima , T. , Shiraishi , M. , Noguchi , M. , Gotoh , M. , Sekiya , T. , Niitani , H. and Shimosato , Y.Myc family gene abnormality in lung cancers and its relation to xenotranspiantability . Cancer Res. , 48 , 6025 – 6028 ( 1988. ). [PubMed] [Google Scholar]

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