Abstract
We previously identified a down-regulation in heterochromatin-associated protein 1 (HP1)(Hsα) expression in MDA-MB-231 breast carcinoma cells (highly invasive/metastatic) compared with MCF-7 cells (poorly invasive/nonmetastatic). In this study, we demonstrate that HP1(Hsα), but not HP1(Hsβ) or HP1(Hsγ) is down-regulated at the mRNA and protein levels in highly invasive/metastatic breast cancer cell lines. In agreement, little to no nuclear HP1(Hsα) staining was observed in these cell lines. In contrast, poorly invasive/nonmetastatic cell lines showed HP1(Hsα) localization to the nucleus and nuclear membrane. Transfection of MDA-MB-231 cells with a green fluorescent protein-HP1(Hsα) expression vector decreased their ability to invade a collagen IV/laminin/gelatin matrix compared with green fluorescent protein-transfected controls. Consistent with the cell culture studies, immunohistochemical analysis of HP1(Hsα) protein localization in distant metastatic tissues from breast cancer patients revealed a decrease in the staining intensity and percentage of cells expressing HP1(Hsα) in seven of nine distant metastatic lesions compared with normal mammary and primary tumors. These results demonstrate a role for HP1(Hsα) in breast cancer invasion and metastasis. Given the role of HP1 in transcriptional silencing in Drosophila, we propose a model in which HP1(Hsα) normally silences genes involved in breast cancer invasion and metastasis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3359-3363 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 60 |
| Issue number | 13 |
| State | Published - Jul 1 2000 |
Funding
ASJC Scopus subject areas
- Oncology
- Cancer Research
