Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Feb;84(4):512–519. doi: 10.1054/bjoc.2000.1632

Expression of individual lamins in basal cell carcinomas of the skin

R S Venables 1, S McLean 1, D Luny 2, E Moteleb 2, S Morley 2, R A Quinlan 3, E B Lane 2, C J Hutchison 4
PMCID: PMC2363768  PMID: 11207047

Abstract

In this study we used a unique collection of type specific anti-lamin antibodies to study lamin expression patterns in normal human skin and in skin derived from patients with basal cell carcinomas (BCCs). Lamin expression in serial sections from frozen tissue samples was investigated by single and double indirect immunofluorescence. In normal skin, lamin A was expressed in dermal fibroblasts and in suprabasal epithelial cells but was absent from all basal epithelial cells. Lamin C was expressed in dermal fibroblasts, suprabasal epithelial cells and a majority of basal epithelial cells. However, lamin C was not expressed in quiescent basal epithelial cells. Lamin B 1 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B 2 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B 2 was expressed in all cell types in normal skin. Lamin expression was also investigated in a collection of 16 BCCs taken from a variety of body sites. Based upon patterns of lamin expression the BCCs were classified into four groups: A-negative (10/16 tumours), C-negative (5/16 tumours), A/C-negative (1/16 tumours) and A/B 2-negative (1/16 tumours). Lamin expression was also compared to cell proliferation index by staining serial sections with the proliferation marker Ki67. 9/10 of the lamin A negative tumours were highly proliferative, whereas 4/5 of the lamin C negative tumours were slow growing. Thus as a general rule absence of lamin A was correlated with rapid growth within the tumour, while absence of lamin C was correlated with slow growth within the tumour. Our data supports the hypothesis that lamin A has a negative influence on cell proliferation and its down regulation may be a requisite of tumour progression. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: nuclear lamins, A-type lamins, B-type lamins, basal cell skin carcinomas

Full Text

The Full Text of this article is available as a PDF (2.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benavente R., Krohne G., Franke W. W. Cell type-specific expression of nuclear lamina proteins during development of Xenopus laevis. Cell. 1985 May;41(1):177–190. doi: 10.1016/0092-8674(85)90072-8. [DOI] [PubMed] [Google Scholar]
  2. Benavente R., KrohneG Change of karyoskeleton during spermatogenesis of Xenopus: expression of lamin LIV, a nuclear lamina protein specific for the male germ line. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6176–6180. doi: 10.1073/pnas.82.18.6176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bridger J. M., Kill I. R., O'Farrell M., Hutchison C. J. Internal lamin structures within G1 nuclei of human dermal fibroblasts. J Cell Sci. 1993 Feb;104(Pt 2):297–306. doi: 10.1242/jcs.104.2.297. [DOI] [PubMed] [Google Scholar]
  4. Broers J. L., Machiels B. M., Kuijpers H. J., Smedts F., van den Kieboom R., Raymond Y., Ramaekers F. C. A- and B-type lamins are differentially expressed in normal human tissues. Histochem Cell Biol. 1997 Jun;107(6):505–517. doi: 10.1007/s004180050138. [DOI] [PubMed] [Google Scholar]
  5. Broers J. L., Ramaekers F. C. Differentiation markers for lung-cancer sub-types. A comparative study of their expression in vivo and in vitro. Int J Cancer Suppl. 1994;8:134–137. doi: 10.1002/ijc.2910570730. [DOI] [PubMed] [Google Scholar]
  6. Broers J. L., Raymond Y., Rot M. K., Kuijpers H., Wagenaar S. S., Ramaekers F. C. Nuclear A-type lamins are differentially expressed in human lung cancer subtypes. Am J Pathol. 1993 Jul;143(1):211–220. [PMC free article] [PubMed] [Google Scholar]
  7. Burke B., Gerace L. A cell free system to study reassembly of the nuclear envelope at the end of mitosis. Cell. 1986 Feb 28;44(4):639–652. doi: 10.1016/0092-8674(86)90273-4. [DOI] [PubMed] [Google Scholar]
  8. Dyer J. A., Kill I. R., Pugh G., Quinlan R. A., Lane E. B., Hutchison C. J. Cell cycle changes in A-type lamin associations detected in human dermal fibroblasts using monoclonal antibodies. Chromosome Res. 1997 Sep;5(6):383–394. doi: 10.1023/a:1018496309156. [DOI] [PubMed] [Google Scholar]
  9. Dyer J. A., Lane B. E., Hutchison C. J. Investigations of the pathway of incorporation and function of lamin A in the nuclear lamina. Microsc Res Tech. 1999 Apr 1;45(1):1–12. doi: 10.1002/(SICI)1097-0029(19990401)45:1<1::AID-JEMT1>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
  10. Farnsworth C. C., Wolda S. L., Gelb M. H., Glomset J. A. Human lamin B contains a farnesylated cysteine residue. J Biol Chem. 1989 Dec 5;264(34):20422–20429. [PMC free article] [PubMed] [Google Scholar]
  11. Furukawa K., Hotta Y. cDNA cloning of a germ cell specific lamin B3 from mouse spermatocytes and analysis of its function by ectopic expression in somatic cells. EMBO J. 1993 Jan;12(1):97–106. doi: 10.1002/j.1460-2075.1993.tb05635.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gerace L., Blobel G. The nuclear envelope lamina is reversibly depolymerized during mitosis. Cell. 1980 Jan;19(1):277–287. doi: 10.1016/0092-8674(80)90409-2. [DOI] [PubMed] [Google Scholar]
  13. Goldberg M., Jenkins H., Allen T., Whitfield W. G., Hutchison C. J. Xenopus lamin B3 has a direct role in the assembly of a replication competent nucleus: evidence from cell-free egg extracts. J Cell Sci. 1995 Nov;108(Pt 11):3451–3461. doi: 10.1242/jcs.108.11.3451. [DOI] [PubMed] [Google Scholar]
  14. Goldman A. E., Moir R. D., Montag-Lowy M., Stewart M., Goldman R. D. Pathway of incorporation of microinjected lamin A into the nuclear envelope. J Cell Biol. 1992 Nov;119(4):725–735. doi: 10.1083/jcb.119.4.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hozák P., Sasseville A. M., Raymond Y., Cook P. R. Lamin proteins form an internal nucleoskeleton as well as a peripheral lamina in human cells. J Cell Sci. 1995 Feb;108(Pt 2):635–644. doi: 10.1242/jcs.108.2.635. [DOI] [PubMed] [Google Scholar]
  16. Jansen M. P., Machiels B. M., Hopman A. H., Broers J. L., Bot F. J., Arends J. W., Ramaekers F. C., Schouten H. C. Comparison of A and B-type lamin expression in reactive lymph nodes and nodular sclerosing Hodgkin's disease. Histopathology. 1997 Oct;31(4):304–312. doi: 10.1046/j.1365-2559.1997.2820881.x. [DOI] [PubMed] [Google Scholar]
  17. Jenkins H., Hölman T., Lyon C., Lane B., Stick R., Hutchison C. Nuclei that lack a lamina accumulate karyophilic proteins and assemble a nuclear matrix. J Cell Sci. 1993 Sep;106(Pt 1):275–285. doi: 10.1242/jcs.106.1.275. [DOI] [PubMed] [Google Scholar]
  18. Kamat A. K., Rocchi M., Smith D. I., Miller O. J. Lamin A/C gene and a related sequence map to human chromosomes 1q12.1-q23 and 10. Somat Cell Mol Genet. 1993 Mar;19(2):203–208. doi: 10.1007/BF01233534. [DOI] [PubMed] [Google Scholar]
  19. Kaufmann S. H., Mabry M., Jasti R., Shaper J. H. Differential expression of nuclear envelope lamins A and C in human lung cancer cell lines. Cancer Res. 1991 Jan 15;51(2):581–586. [PubMed] [Google Scholar]
  20. Lanoix J., Skup D., Collard J. F., Raymond Y. Regulation of the expression of lamins A and C is post-transcriptional in P19 embryonal carcinoma cells. Biochem Biophys Res Commun. 1992 Dec 30;189(3):1639–1644. doi: 10.1016/0006-291x(92)90265-m. [DOI] [PubMed] [Google Scholar]
  21. Lebel S., Lampron C., Royal A., Raymond Y. Lamins A and C appear during retinoic acid-induced differentiation of mouse embryonal carcinoma cells. J Cell Biol. 1987 Sep;105(3):1099–1104. doi: 10.1083/jcb.105.3.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lehner C. F., Stick R., Eppenberger H. M., Nigg E. A. Differential expression of nuclear lamin proteins during chicken development. J Cell Biol. 1987 Jul;105(1):577–587. doi: 10.1083/jcb.105.1.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Machiels B. M., Broers J. L., Raymond Y., de Ley L., Kuijpers H. J., Caberg N. E., Ramaekers F. C. Abnormal A-type lamin organization in a human lung carcinoma cell line. Eur J Cell Biol. 1995 Aug;67(4):328–335. [PubMed] [Google Scholar]
  24. Machiels B. M., Zorenc A. H., Endert J. M., Kuijpers H. J., van Eys G. J., Ramaekers F. C., Broers J. L. An alternative splicing product of the lamin A/C gene lacks exon 10. J Biol Chem. 1996 Apr 19;271(16):9249–9253. doi: 10.1074/jbc.271.16.9249. [DOI] [PubMed] [Google Scholar]
  25. Mittnacht S., Weinberg R. A. G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell. 1991 May 3;65(3):381–393. doi: 10.1016/0092-8674(91)90456-9. [DOI] [PubMed] [Google Scholar]
  26. Nigg E. A. The nuclear envelope. Curr Opin Cell Biol. 1989 Jun;1(3):435–440. doi: 10.1016/0955-0674(89)90002-1. [DOI] [PubMed] [Google Scholar]
  27. Ozaki T., Saijo M., Murakami K., Enomoto H., Taya Y., Sakiyama S. Complex formation between lamin A and the retinoblastoma gene product: identification of the domain on lamin A required for its interaction. Oncogene. 1994 Sep;9(9):2649–2653. [PubMed] [Google Scholar]
  28. Paulin-Levasseur M., Giese G., Scherbarth A., Traub P. Expression of vimentin and nuclear lamins during the in vitro differentiation of human promyelocytic leukemia cells HL-60. Eur J Cell Biol. 1989 Dec;50(2):453–461. [PubMed] [Google Scholar]
  29. Pugh G. E., Coates P. J., Lane E. B., Raymond Y., Quinlan R. A. Distinct nuclear assembly pathways for lamins A and C lead to their increase during quiescence in Swiss 3T3 cells. J Cell Sci. 1997 Oct;110(Pt 19):2483–2493. doi: 10.1242/jcs.110.19.2483. [DOI] [PubMed] [Google Scholar]
  30. Rowlands D. C., Bunce C. M., Crocker J., Ayres J. G., Johnson G. D., Ling N., Brown G. Expression of a nuclear envelope protein recognized by the monoclonal antibody BU31 in lung tumours: relationship to Ki-67 antigen expression. J Pathol. 1994 Jun;173(2):89–96. doi: 10.1002/path.1711730204. [DOI] [PubMed] [Google Scholar]
  31. Röber R. A., Weber K., Osborn M. Differential timing of nuclear lamin A/C expression in the various organs of the mouse embryo and the young animal: a developmental study. Development. 1989 Feb;105(2):365–378. doi: 10.1242/dev.105.2.365. [DOI] [PubMed] [Google Scholar]
  32. Schatten G., Maul G. G., Schatten H., Chaly N., Simerly C., Balczon R., Brown D. L. Nuclear lamins and peripheral nuclear antigens during fertilization and embryogenesis in mice and sea urchins. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4727–4731. doi: 10.1073/pnas.82.14.4727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stewart C., Burke B. Teratocarcinoma stem cells and early mouse embryos contain only a single major lamin polypeptide closely resembling lamin B. Cell. 1987 Nov 6;51(3):383–392. doi: 10.1016/0092-8674(87)90634-9. [DOI] [PubMed] [Google Scholar]
  34. Stick R., Hausen P. Changes in the nuclear lamina composition during early development of Xenopus laevis. Cell. 1985 May;41(1):191–200. doi: 10.1016/0092-8674(85)90073-x. [DOI] [PubMed] [Google Scholar]
  35. Templeton D. J., Park S. H., Lanier L., Weinberg R. A. Nonfunctional mutants of the retinoblastoma protein are characterized by defects in phosphorylation, viral oncoprotein association, and nuclear tethering. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3033–3037. doi: 10.1073/pnas.88.8.3033. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES