Journal article
Down-regulation of HP1Hsα expression is associated with the metastatic phenotype in breast cancer
Cancer research (Chicago, Ill.), Vol.60(13), pp.3359-3363
2000
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 HP1Hsα, but not HP1Hsβ or HP1Hsγ, is down-regulated at the mRNA and protein levels in highly invasive/metastatic breast cancer cell lines. In agreement, little to no nuclear HP1Hsα staining was observed in these cell lines. In contrast, poorly invasive/nonmetastatic cell lines showed HP1Hsα localization to the nucleus and nuclear membrane. Transfection of MDA-MB-231 cells with a green fluorescent protein-HP1Hsα 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 HP1Hsαprotein localization in distant metastatic tissues from breast cancer patients revealed a decrease in the staining intensity and percentage of cells expressing HP1Hsα in seven of nine distant metastatic lesions compared with normal mammary and primary tumors. These results demonstrate a role for HP1Hsα in breast cancer invasion and metastasis. Given the role of HP1 in transcriptional silencing in Drosophila, we propose a model in which HP1Hsα normally silences genes involved in breast cancer invasion and metastasis.
Details
- Title: Subtitle
- Down-regulation of HP1Hsα expression is associated with the metastatic phenotype in breast cancer
- Creators
- Dawn A Kirschmann - Department of Anatomy and Cell Biology, College of Medicine, University of Iowa Cancer Center, University of Iowa, Iowa City, Iowa 52242-1109, United StatesRuth A Lininger - University of North Carolina School of MedicineLynn M. G Gardner - Department of Anatomy and Cell Biology, College of Medicine, University of Iowa Cancer Center, University of Iowa, Iowa City, Iowa 52242-1109, United StatesElisabeth A Seftor - Department of Anatomy and Cell Biology, College of Medicine, University of Iowa Cancer Center, University of Iowa, Iowa City, Iowa 52242-1109, United StatesValerie A Odero - Department of Anatomy and Cell Biology, College of Medicine, University of Iowa Cancer Center, University of Iowa, Iowa City, Iowa 52242-1109, United StatesAlexandra M Ainsztein - University of EdinburghWilliam C Earnshaw - University of EdinburghLori L Wallrath - University of IowaMary J. C Hendrix - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.60(13), pp.3359-3363
- Publisher
- American Association for Cancer Research
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2000
- Academic Unit
- Biochemistry and Molecular Biology; University College Courses
- Record Identifier
- 9984293555702771
Metrics
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