Constitutional abnormality of nuclear membrane proteins in small cell lung carcinoma
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Nuclear membrane proteins reportedly play important roles in maintaining nuclear structures and coordinating cell activities. Studying profiles of nuclear membrane proteins may help us evaluate the biological and/or clinical nature of malignant tumors. Using immunohistochemistry with antibodies for emerin, lamin A/C, lamin B, and LAP2, we examined 105 lung cancer tissues from 33 small cell lung carcinomas (SCLCs) and 72 non-SCLCs (34 adenocarcinomas, 30 squamous cell carcinomas, and 8 large cell carcinomas). Emerin had negative or local/weak positivity in 79% of SCLCs and 1% of non-SCLCs, and lamin A/C had similar positivity in 91% of SCLCs and 3% of non-SCLCs. LAP2’s expression was similar between SCLCs and non-SCLCs. RT-PCR analyses for these four nuclear membrane proteins over 7 cell lines showed that mRNA of emerin and lamin A/C were distinctly downregulated in the SCLC cell lines, supporting the immunohistochemical results. In conclusion, we suggest that downregulation of the nuclear membrane proteins emerin and lamin A/C is characteristic of SCLC cells, and this constitutional abnormality of the nuclear membrane may be related to the biological and/or clinical nature of SCLC. In addition, knowing the nuclear protein profile in SCLC cells may contribute to our understanding of nuclear fragility known as the crush artifact in pulmonary biopsy specimens.
KeywordsNuclear membrane proteins Lung carcinoma Immunohistochemistry Polymerase chain reaction (PCR)
The authors thank Ms. Mikiko Yoda, Ms. Miyuki Ito, Mr. Yoshihito Koshimizu, and Ms. Wakaba Iha for technical support and Ms. Kayoko Kono for executive assistance.
Wang Jieying, Tetsuo Kondo, and Ryohei Katoh conceived and designed the study, and wrote, edited, and reviewed the manuscript. Wang Jieying and Tetsuo Kondo performed the experiment. Tadao Nakazawa, Naoki Oishi, and Kunio Mochizukia researched and analyzed data. All authors gave final approval for publication.
This study was funded by the Natural Science Foundation of Shaanxi Provincial Department of Education (grant number 18JK0666).
Compliance with ethical standards
The study protocols were approved by the Institutional Ethics Board of the University of Yamanashi, Yamanashi, Japan. The study complies with all ethical standards as stated in the Ethical Responsibilities of Authors on the Virchows Archiv webpage (https://www.springer.com/medicine/pathology/journal/428).
Conflict of interest
The authors declare that they have no conflicts of interest.
- 13.Holaska JM, Wilson KL (2007) An emerin “proteome”: purification of distinct emerin-containing complexes from HeLa cells suggests molecular basis for diverse roles including gene regulation, mRNA splicing, signaling, mechanosensing, and nuclear architecture. Biochemistry 46:8897–8908. https://doi.org/10.1021/bi602636m CrossRefGoogle Scholar
- 16.Idowu MO, Powers CN (2010) Lung cancer cytology: potential pitfalls and mimics. Int J Clin Exp Pathol 3:367–385Google Scholar
- 17.Davidson MR, Gazdar AF, Clarke BE (2013) The pivotal role of pathology in the management of lung cancer. J Thorac Dis 5:S463–S478. https://doi.org/10.3978/j.issn.2072-1439.2013.08.43 Google Scholar
- 18.Travis WD, Muller-Hermelink HK et al (2004) Pathology and genetics of tumours of the lung, pleura, thymus and heart. WHO/IASLC classification of lung and pleural tumours. IARC Press, LyonGoogle Scholar
- 19.Ganti AK, West WW, Lackner RP, Kessinger A (2010) Current concepts in the diagnosis and management of small-cell lung cancer. Oncology 24:1034–1039Google Scholar
- 20.Cohen MH, Matthews MJ (1978) Small cell bronchogenic carcinoma: a distinct clinicopathologic entity. Semin Oncol 5:234–243Google Scholar
- 21.Ganti AK, West WW, Zhen W (2013) Current concepts in the management of small cell lung cancer. Indian J Med Res 137:1043–1051Google Scholar
- 26.Coradeghini R, Barboro P, Rubagotti A, Boccardo F, Parodi S, Carmignani G, D’Arrigo C, Patrone E, Balbi C (2006) Differential expression of nuclear lamins in normal and cancerous prostate tissues. Oncol Rep 15:609–613Google Scholar
- 31.Kaufmann SH, Mabry M, Jasti R, Shaper JH (1991) Differential expression of nuclear envelope lamins A and C in human lung cancer cell lines. Cancer Res 51:6Google Scholar
- 32.Broers JL, Raymond Y, Rot MK, Kuijpers H, Wagenaar SS, Ramaekers FC (1993) Nuclear A-type lamins are differentially expressed in human lung cancer subtypes. Am J Pathol 143:211–220Google Scholar
- 33.Machiels BM, Broers JL, Raymond Y, de Ley L, Kuijpers HJ, Caberg NE, Ramaekers FC (1995) Abnormal A-type lamin organization in a human lung carcinoma cell line. Eur J Cell Biol 67:328–335Google Scholar
- 34.Christopher DMF (2007) Diagnostic histopathology of tumors. In: Cesar AM, Saul S (eds) Tumor of the lung and pleura,3 edn. 189Google Scholar
- 37.Zwerger M, Ho CY, Lammerding J (2011) Nuclear mechanics in disease. Annu Rev Biomed Eng 13:397–428. https://doi.org/10.1146/annurev-bioeng-071910-124736 CrossRefGoogle Scholar