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The clinicopathological significance of lamin A/C, lamin B1 and lamin B receptor mRNA expression in human breast cancer

Abstract

Lamin A/C (LMNA), lamin B1 (LMNB1) and lamin B receptor (LBR) have key roles in nuclear structural integrity and chromosomal stability. In this study, we have studied the relationships between the mRNA expressions of A-type lamins, LMNB1 and LBR and the clinicopathological parameters in human breast cancer. Samples of breast cancer tissues (n = 115) and associated non-cancerous tissue (ANCT; n = 30) were assessed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher levels of A-type lamins and LMNB1 mRNA expression were seen in ANCT. Higher lamin A/C expression was associated with the early clinical stage (TNM1 vs. TNM3 — 13 vs. 0.21; p = 0.0515), with better clinical outcomes (disease-free survival vs. mortality — 11 vs. 1; p = 0.0326), and with better overall (p = 0.004) and disease-free survival (p = 0.062). The expression of LMNB1 declined with worsening clinical outcome (disease-free vs. mortalities — 0.0011 vs. 0.000; p = 0.0177). LBR mRNA expression was directly associated with tumor grade (grade 1 vs. grade 3 — 0.00 vs. 0.00; p = 0.0479) and Nottingham Prognostic Index (NPI1 vs. NPI3 — 0.00 vs. 0.00; p = 0.0551). To the best of our knowledge, this is the first study to suggest such a role for A-type lamins, lamin B1 and LBR in human breast cancer, identifying an important area for further research.

Abbreviations

CI:

confidence interval

CK19:

cytokeratin 19

DF:

disease-free survival

DR:

distant disease recurrence

LBR:ANCT:

associated non-cancerous tissue, lamin B receptor

LMDM:

lamin B deficient micro-domains

LR:

local disease recurrence

mTOR:

mammalian target of rapamycin

NPI:

Nottingham Prognostic Index

qPCR:

quantitative polymerase chain reaction

TNM:

clinical stage according to tumor size, nodal status and presence of distant metastases

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Correspondence to Kefah Mokbel.

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Wazir, U., Ahmed, M.H., Bridger, J.M. et al. The clinicopathological significance of lamin A/C, lamin B1 and lamin B receptor mRNA expression in human breast cancer. Cell Mol Biol Lett 18, 595–611 (2013). https://doi.org/10.2478/s11658-013-0109-9

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Key words

  • Lamin A/C
  • Lamin B
  • Lamin B receptor
  • Breast cancer
  • qPCR
  • Chromosomal instability
  • Cell senescence
  • Cell cycle
  • DNA repair
  • Ageing