Journal article
Down-regulation of HP1(Hs alpha) expression is associated with the metastatic phenotype in breast cancer
Cancer research (Chicago, Ill.), Vol.60(13), pp.3359-3363
07/01/2000
PMID: 10910038
Abstract
We previously identified a down regulation in heterochromatin-associated protein 1 (HP1)(Hs alpha) 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(Hs alpha), but not HP1(Hs beta) or HP1(Hs gamma), Is down-regulated at the mRNA and protein levels in highly invasive/metastatic breast cancer cell lines. In agreement, little to no nuclear HP1(Hs alpha) staining was observed in these cell lines. In contrast, poorly Invasive/nonmetastatic cell lines showed HP1(Hs alpha) localization to the nucleus and nuclear membrane, Transfection of MDA-MB-231 cells with a green fluorescent protein-HP1(Hs alpha) 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(Hs alpha) protein localization in distant metastatic tissues from breast cancer patients revealed a decrease in the staining intensity and percentage of cells expressing HP1(Hs alpha) in seven of nine distant metastatic lesions compared with normal mammary and primary tumors. These results demonstrate a role for HP1(Hs alpha) In breast cancer invasion and metastasis. Given the role of HP1 in transcriptional silencing In Drosophila, we propose a model in which HP1(Hs alpha) normally silences genes involved in breast cancer invasion and metastasis.
Details
- Title: Subtitle
- Down-regulation of HP1(Hs alpha) expression is associated with the metastatic phenotype in breast cancer
- Creators
- D A KirschmannR A LiningerLMG GardnerE A SeftorV A OderoA M AinszteinW C EarnshawL L WallrathMJC Hendrix
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.60(13), pp.3359-3363
- Publisher
- Amer Assoc Cancer Research
- PMID
- 10910038
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Number of pages
- 5
- Grant note
- 073915 / Wellcome Trust; European Commission R37CA059702 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) CA59702 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 07/01/2000
- Academic Unit
- Biochemistry and Molecular Biology; University College Courses
- Record Identifier
- 9984293081602771
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