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. 2013 Nov 30;18(4):595–611. doi: 10.2478/s11658-013-0109-9

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

Umar Wazir 1,2, Mai Hassan Ahmed 3,4, Joanna M Bridger 3, Amanda Harvey 4, Wen G Jiang 5, Anup K Sharma 1, Kefah Mokbel 1,2,6,✉
PMCID: PMC6275779  PMID: 24293108

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.

Key words: Lamin A/C, Lamin B, Lamin B receptor, Breast cancer, qPCR, Chromosomal instability, Cell senescence, Cell cycle, DNA repair, Ageing

Full Text

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Abbreviations used

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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