Abstract P6-04-14: mRNA expressions of lamin B1 and lamin B receptor: Clinical correlations with human breast cancer

Abstract

BACKGROUND: Lamin B (LMNB) and lamin B receptor (LBR) are key components of the nuclear envelope, with roles in chromosomal stability, DNA repair, and cell differentiation. Lamins provide structural support to the nuclear envelope, while LBR is believed to anchor lamin B to the envelope. In addition, LBR also has a number of downstream mediators which affect cell cycle and cell differentiation. Classically, they have been implicated in a spectrum of largely congenital ailments including certain forms of muscle dystrophy and progeria. These conditions are collectively referred to as “laminopathies”. More recently, defects in the expression of lamins have been implicated in neoplasias of the colon, prostate, liver and ovaries. In this study, we have endeavoured to elucidate the relationships between the mRNA expressions of LMNB1 and LBR and the clinicopathological parameters of human breast cancer. METHODS: Breast cancer tissues (n = 115) and associated non-cancerous tissue (ANCT) (n = 30) underwent reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. RESULTS: LMNB1 mRNA expression was higher in ANCT as compared to cancerous tissue (ANCT vs. cancerous tissue: 0.12 vs. 0.00; p = <0.0001). This difference remained highly significant in all patient categories by tumour grade and clinical stage. In addition, the expression of LMNB1 declined with worsening clinical outcome. This association was statistically significant when comparing patient with disease-free survival with disease related mortalities (Disease-free vs. mortalities: 0.0011 vs. 0.000; p = 0.0177). LBR mRNA expression was found to be directly associated with tumour grade (grade 1 vs.3: 0.00 vs. 0.00; p = 0.0479) and the Nottingham Prognostic Index (NPI1 vs. 3: 0.00 vs. 0.00; p = 0.0551). CONCLUSIONS: To our knowledge, this is the first study to suggest such a role for LMNB1 and LBR in human breast cancer. The contrasting relationships of LMNB1 and LBR expressions with the clinicopathological parameters of human breast cancer may suggest that disruptions in the physiologically normal interactions between these molecules in the nuclear envelope may serve as pathway leading towards the pathogenesis of human breast cancer. Potentially this may be a significant pathway requiring further investigation to be better understood, in order to identify further potential areas for therapeutic intervention. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-04-14.

Expression of Therapy-Induced Senescence Markers in Breast Cancer Samples Upon Incomplete Response to Neoadjuvant Chemotherapy

“…Finally, several previous studies reported that the expression of senescence biomarkers correlated with poor outcomes in different kinds of cancers such as breast, colon, and bone cancer [ 35 , 71–73 ]. In addition to determining the extent of senescence induction in vivo , the exact role of senescence in determining the outcome of therapy is still debatable [ 74 ].…”