Subcellular Localization of Maspin Correlates with Histone Deacetylase 1 Expression in Human Breast Cancer.

Maspin is known to be a tumor suppressor protein. Its nuclear localization and endogenous inhibition of histone deacetylase 1 (HDAC1) are considered crucial for its tumor suppressor activity. However, it remains unclear whether subcellular localization of maspin correlates with HDAC1 expression level in human breast cancer.

Immunohistochemical analyses were performed on 164 resected specimens of invasive breast carcinoma using antibodies for maspin and HDAC1. Subcellular localization of maspin protein and HDAC1 mRNA expression level in two human breast cancer cell lines (MCF7, MDA-MB-231) and mammary epithelial cell line (MCF10) were analyzed by immunofluorescence and quantitative polymerase chain reaction, respectively.

The frequency of cytoplasmic-only, pancellular (combined nuclear and cytoplasm) and no staining of maspin were 31%, 14.0% and 55%, respectively. The cytoplasmic-only subgroup showed significantly higher histological grade (p=0.004), negative progesterone receptor status (p=0.003) and shorter disease-free survival compared to the pancellular subgroup (p=0.043). High HDAC1 expression was observed in 60% of cases and was significantly correlated with cytoplasmic-only staining compared to pancellular (p<0.001) or no staining (p=0.004). Immunofluorescence analysis revealed that maspin protein was localized mainly in the cytoplasm in MCF7 and MDA-MB-231 cells, while in both the nucleus and cytoplasm in MCF10A cells. HDAC1 mRNA levels were significantly up-regulated in MCF7 and MDA-MB-231 cells compared to MCF10A cells (p<0.001).

High HDAC1 expression may contribute to the aggressiveness of human breast cancer with cytoplasmic-only expression of maspin.