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Com-1/P8 in oestrogen regulated growth of breast cancer cells, the ER-β connection
- Source :
-
Biochemical & Biophysical Research Communications . Apr2005, Vol. 330 Issue 1, p253-262. 10p. - Publication Year :
- 2005
-
Abstract
- Abstract: Background: Com-1 is a molecule that has recently discovered to have putative action on the metastatic nature of cancer cells. The current study investigated the impact of Com-1 on oestrogen regulated cell growth of breast cancer cells and explored the potential link between Com-1 and ER-β. Method: Full length Com-1 cDNA was isolated from normal mammary tissues. Ribozyme transgenes that specifically targeted human Com-1 were constructed using the pEF6/V5-His vector. Expression of Com-1 was assessed at both mRNA and protein levels. Interaction of Com-1 with other candidate molecules was studied using immunoprecipitation and Western blotting. Results: Elimination of Com-1 by way of ribozyme transgenes results in breast cancer cells with increased rate of growth and increased invasive potential. In contrast, over-expression of Com-1 in the cancer cells had an opposite effect. In ER-α-negative/ER-β positive MDA MB-231 cells, elimination of Com-1 caused more vigorous growth in response to 17-β-estradiol. However, the effect of Com-1 modification on MCF-7, which is positive for both ER-α and ER-β, was less clear. Protein interaction analysis has indicated that the Com-1 and ER-β were mutually co-precipitated with each other in breast cancer cells. Immunocytochemical staining revealed that Com-1 was primarily present in the nucleus, with some degree of cytoplasmic staining, and that the distribution of Com-1 was identical to that of ER-β. 17-β-Estradiol stimulation resulted in reduction of nucleic staining of Com-1. This reduction of nucleic Com-1 can be reverted when ubiquitin inhibitor, ubiquitin aldehyde or the lactacystin proteosome inhibitor was present, suggesting a pivotal role of the ubiquitin–proteosome pathway in the Com-1/ER-β complex. Conclusion: Com-1 plays a tumour suppressor role in breast cancer cells and is involved in oestrogen-regulated cell growth. This action is potentially exerted by interacting with ER-β, in human breast cancer cells. The fate of Com-1 can be dually regulated by oestrogen and ubiquitin pathway. [Copyright &y& Elsevier]
- Subjects :
- *CANCER cells
*GROWTH factors
*BREAST cancer
*STEROID hormones
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 330
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 16769960
- Full Text :
- https://doi.org/10.1016/j.bbrc.2005.02.157