Article

Effects of raloxifene on caveolin-1 mRNA and protein expressions in vascular smooth muscle cells.

Institute of Biochemistry and Molecular Biology, Medical College, Shandong University, Jinan 250012, China.
Acta Biochimica et Biophysica Sinica (Impact Factor: 1.81). 12/2006; 38(11):747-52. DOI: 10.1111/j.1745-7270.2006.00222.x
Source: PubMed

ABSTRACT Caveolin-1 is regulated by estrogen in vascular smooth muscle cells. Raloxifene, a selective estrogen receptor modulator that possibly has cardioprotective properties without an increased risk of cancer or other side effects of estrogen, may be used in women with risk of coronary artery disease. However, the relationship between raloxifene and caveolin-1 is still unknown. Therefore, this study was designed to see whether raloxifene regulates caveolin-1 expression and if so, whether such regulation is mediated by estrogen receptor. Rat aortic smooth muscle cells were cultured in the absence or presence of raloxifene (10(8-) to 10(6-) M) for 12 or 24 h. Both mRNA and protein levels of caveolin-1 were increased significantly after 24 h treatment with raloxifene. These increases were inhibited by estrogen receptor antagonist ICI 182780 (10(5-) M). Results of this study suggest that raloxifene stimulates caveolin-1 transcription and translation through estrogen receptor mediated mechanisms.

0 Bookmarks
 · 
53 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aims of this study were to define the distribution of caveolin 2 (CAV2) in frozen and formalin fixed, paraffin embedded (FFPE) normal breast samples and the significance of CAV2 expression in breast cancer. Caveolin 2 distribution in frozen and paraffin-embedded whole tissue sections of normal breast was evaluated using immunohistochemistry and immunofluorescence, in conjunction with antibodies to define luminal epithelial cells (oestrogen receptor and cytokeratin 8/18) and myoepithelial/ basal cells (cytokeratins 14 and 5/6, p63 and smooth muscle actin). CAV2 expression was also immunohistochemically analysed in two independent cohorts of invasive breast carcinomas (n = 245 and n = 418). In normal breast, CAV2 was expressed in myoepithelial cells, endothelial cells, fibroblasts and adipocytes. Luminal epithelial cells showed no or only negligible staining. CAV2 expression was observed in 9.6% of all breast cancers and was strongly correlated with high histological grade, lack of oestrogen receptor, progesterone receptor and cyclin D1 expression, and positivity for epidermal growth factor receptor, basal markers, p53 expression, and high proliferation index. Furthermore, CAV2 expression was significantly associated with basal-like immunophenotype and proved to be a prognostic factor for breast cancer-specific survival on univariate analysis. Our results demonstrate that CAV2 is preferentially expressed in basal-like cancers and is associated with poor prognosis. Further in vitro studies are required to determine whether CAV2 has oncogenic properties or is only a surrogate marker of basal-like carcinomas.
    Breast Cancer Research and Treatment 08/2008; 110(2):245-56. · 4.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ICI182,780 is used in adjuvant therapies of breast cancer. As a complete estrogen receptor (ER) blocker, ICI182,780 may antagonize the effects of estrogen on the cardiovascular system. Estrogen inhibits the proliferation of vascular smooth muscle cells (VSMCs), which is one of the mechanisms that estrogen can exert cardioprotective effects. In the present study, to assess the effects of ICI182,780 on the proliferation of VSMCs, we cultured VSMCs isolated from rat aorta with or without the ER antagonist ICI182,780. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, bromodeoxyuridine incorporation assay, viable cell count, immunochemical staining for proliferating cell nuclear antigen (PCNA), and S-phase ratio determined by flow cytometry revealed a remarkable proliferation of VSMCs after ICI182,780 treatment. ICI182,780 significantly enhanced cell growth in a dose-dependent manner (10(-8)-10(-5) M). Furthermore, the number of PCNA-positive cells and the S-phase progression of VSMCs increased after treatment with ICI182,780. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis showed that the mRNA and protein level of cyclin D1 in VSMCs increased under the treatment of ICI182,780. These data suggested that ICI182,780 can promote the growth of VSMCs, which might produce some adverse effects on the cardiovascular system.
    Acta Biochimica et Biophysica Sinica 02/2011; 43(2):118-23. · 1.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Caveolae are small plasma membrane invaginations that have been implicated in a variety of functions including transcytosis, potocytosis and cholesterol transport and signal transduction. The major protein component of this compartment is a family of proteins called caveolins. Experimental data obtained in knockout mice have provided unequivocal evidence for a requirement of caveolins to generate morphologically detectable caveolae structures. However, expression of caveolins is not sufficient per seto assure the presence of these structures. With respect to other roles attributed to caveolins in the regulation of cellular function, insights are even less clear. Here we will consider, more specifically, the data concerning the ambiguous roles ascribed to caveolin-1 in signal transduction and cancer. In particular, evidence indicating that caveolin-1 function is cell context dependent will be discussed.
    Journal of Cellular and Molecular Medicine 08/2008; 12(4):1130-50. · 4.75 Impact Factor

Full-text

View
0 Downloads