Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker in patients with breast cancer

Abstract

BackgroundPolycomb Group (PcG) proteins are epigenetic silencers involved in maintaining cellular identity, and their deregulation can result in cancer. Expression of Mel-18 and Bmi-1 has been studied in tumor tissue, but not in adjacent non-cancerous breast epithelium. Our study compares the expression of the two genes in normal breast epithelium of cancer patients and relates it to the level of expression in the corresponding tumors as well as in breast epithelium of healthy women.MethodsA total of 79 tumors, of which 71 malignant tumors of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared to the reduction mammoplastic specimens of 11 healthy women. In addition there was available adjacent cancer free tissue for 23 of the malignant tumors. The tissue samples were stored in RNAlater, RNA was isolated to create expression microarray profile. These two genes were then studied more closely first on mRNA transcription level by microarrays (Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein expression level using immunohistochemistry.ResultsBmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients. Conversely, mRNA transcription level of Mel-18 is lower in normal breast from patients operated for breast cancer compared to breast tissue from mammoplasty. When protein expression of these two genes was evaluated, we observed that most of the epithelial cells were positive for Bmi-1 in both groups of tissue samples, although the expression intensity was stronger in normal tissue from cancer patients compared to mammoplasty tissue samples. Protein expression of Mel-18 showed inversely stronger intensity in tissue samples from mammoplasty compared to normal breast tissue from patients operated for breast cancer.ConclusionBmi-1 mRNA level is consistently increased and Mel-18 mRNA level is consistently decreased in adjacent normal breast tissue of cancer patients as compared to normal breast tissue in women having had reduction mammoplasties. Bmi-1/Mel-18 ratio can be potentially used as a tool for stratifying women at risk of developing malignancy.

In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2

“…In view of the low expression of Ezh2 in normal resting populations, selective pharmacological intervention to inhibit Ezh2 activity in both wild type and mutant lymphomas is a promising approach that warrants further research. Mel-18 expression was previously reported in several normal adult tissues [15][16][17]. In RLH, we found that few cells expressed Mel-18 with moderate intensity while some populations expressed…”

“…The upregulation of Bmi-1 was reported in a variety of cancers, and sometimes correlated with a poor prognosis [6,[12][13][14]. Mel-18/PCGF2 is a component of the PRC1.2 complex, and was previously described as a tumor suppressor that is expressed in the normal state and suppressed in neoplastic conditions in gastric, prostate and breast cancers [15][16][17].…”

HSP90 inhibits apoptosis and promotes growth by regulating HIF-1α abundance in hepatocellular carcinoma

“…of ----------------------------------Clinicopathological patients, HSP90- Immunohistochemical analysis. IHC was performed on 5-µm-thick sections from formalin-fixed, paraffin-embedded tissue samples applied to coated slides, as described in a previous study (16). The following antibodies were used together with a streptavidin-peroxidase (SP) conjugate (SP-IHC method): HSP90 (ab13492; 1:150) and HIF-1α (ab85886; 1:200) (both from Abcam, Cambridge, MA, USA).…”

MEL-18 loss mediates estrogen receptor–α downregulation and hormone independence

“…Previous studies, including our own, have demonstrated that MEL-18 expression is lower in human breast cancer tissues than in normal breast tissues (9,10,14), but the clinical importance of MEL-18 in different breast cancer subtypes has not been evaluated. In this study, based on IHC analysis of breast cancer specimens and the gene expression profiles of multiple independent microarray datasets from various breast cancer cohorts, we demonstrated a negative correlation of MEL-18 Therefore, these data indicate the importance of MEL-18-mediated SENP1 regulation in breast cancer progression and suggest SENP1 and MEL-18 as markers of ER-α negativity.…”

“…Although further clinical evidence is needed, accumulating studies have suggested that MEL-18 acts as a tumor suppressor in several human tumors, including breast cancer (7)(8)(9)(10)(11). Our previous studies have also revealed that MEL-18 loss facilitates stem cell activity, cell growth, angiogenesis, and epithelial-mesenchymal transition (EMT) in breast cancer (12)(13)(14)(15), implying an association of MEL-18 loss with an aggressive phenotype.…”