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Raquel Soares

Publications and source records attributed to Raquel Soares.

12 recordsLinked to original sources
PubMed2007

Elucidating progesterone effects in breast cancer: cross talk with PDGF signaling pathway in smooth muscle cell.

Several studies indicate that progesterone exerts relevant effects in breast tissue. However, the exact role of this steroid in breast cancer development and progression has not been elucidated. Here, we show that platelet-derived growth factor (PDGF)-A is one of the progesterone target genes on breast cancer MCF7 and T47D cells. A paracrine role for PDGF-A was investigated, since its receptor expression was down-regulated from breast cancer cells. Progesterone increased PDGF-A protein release as evaluated by Western blotting and ELISA. Medium from Progesterone-treated MCF7 cells resulted in phosphorylation of smooth muscle cells PDGF receptor alpha. This effect was not observed after treatment with PDGF inhibitor. MCF7 cells-secreted PDGF-A was able to increase smooth muscle cell viability and proliferation and decrease apoptosis, effects that were prevented by the use of a PDGF-A neutralizing antibody. Notably, cell invasion was not influenced by PDGF-A secreted by MCF7 cells. Our results elucidated for the first time the cross talk between progesterone and PDGF signaling pathway. The fact that MCF7-secreted PDGF elicited crucial roles in vascular wall smooth muscle cells, suggested a paracrine pathway for progesterone. Targeting these progesterone-induced processes may provide novel therapeutic strategies for hormone-dependent human breast cancer.

Apoptosis↗
PubMed2006

Distinct modulation of alkaline phosphatase isoenzymes by 17beta-estradiol and xanthohumol in breast cancer MCF-7 cells.

OBJECTIVES: To examine the effect of 17beta-estradiol and xanthohumol in alkaline phosphatase (ALP) expression and activity in breast cancer MCF-7 cells. DESIGN AND METHODS: ALP isoenzymes expression was evaluated by RT-PCR and Western blotting. ALP activity was measured by spectrophotometry. Cell proliferation and apoptosis were examined by MTT and immunostaining for KI67 and TUNEL, respectively. RESULTS: ALP isoenzymes expression and activity were decreased by 1 nM 17beta-estradiol. Pure estrogenic antagonist (ICI 182,780) reversed 17beta-estradiol-inhibiting effect in TNS-ALP expression. RNA and protein expression of IALP, but not TNS-ALP, was also decreased by incubation with 10 microM xanthohumol (IC(50)) and was accompanied by a significant reduction in ALP activity. Treatment with 17beta-estradiol enhanced cell proliferation and decreased apoptosis. Conversely, xanthohumol incubation inhibited cell viability and apoptosis. CONCLUSION: Estrogens and xanthohumol differently modulate ALP isoenzymes. ALP loss associated with increased cell proliferation. Modulation of this enzyme by 17beta-estradiol and xanthohumol might provide therapeutic strategies against hormone-dependent breast cancer.

Alkaline Phosphatase↗
PubMed2004

Glutathione S-transferase genotype GSTM1 as a predictor of elevated angiogenic phenotype in patients with early onset breast cancer.

The genes coding for separate isoforms of both the human glutathione-S-transferase class (GST) mu and class theta enzymes (GSTM1 and GSTT1) are polymorphic with a percentage of normal individuals exhibiting a homozygous deletion of the genes. An association between glutathione, proliferation and tumour angiogenesis has been observed. The aim of the present study was to analyse GST polymorphisms and to determine its correlation with the angiogenesis status of the tumoral tissue of patients with breast cancer. For each case, immunohistochemistry of tumour tissue and DNA genotyping by PCR on genomic DNA isolated from blood cells were performed. The mean intratumoral microvessel density (MVD index) was higher for the cases with GSTM1 wild-type genotype in comparison with the cases with the GSTM1-null genotype (89.6 +/- 10.0 vs. 60.9 +/- 6.7; P = 0.022). This was even more evident for women with a breast cancer onset before the age of 35 (106.9 +/- 11.9 vs. 61.8 +/- 9.8; P =0.011). Multivariate logistic regression analysis of GSTM1 and GSTT1 genotypes, histologic grade, axillary node status and age at diagnosis demonstrate the independent association between GSTM1 genotypes and angiogenesis and the association of GSTM1 -wild type genotype with high MVD index (adjusted OR = 5.98, 95% CI 1.28-28.10, P = 0.023). A role of this enzyme in the hypoxia-induced metabolic pathway can be a connection for its association with angiogenesis. Further studies on the enzymatic components of the glutathione biosynthetic pathway in other cancers could define a pharmacogenomic profile of human neoplasia and help identify targets for the development of therapeutic strategies.

Adult↗
PubMed2003

17 beta -estradiol-mediated vessel assembly and stabilization in tumor angiogenesis requires TGF beta and EGFR crosstalk.

It is widely established that angiogenesis is required during tumor progression. Emerging data, suggests that estrogens can mediate endothelial proliferation and differentiation. We investigated the role of estrogens in the formation and stabilization of capillary-like structures, and identified 17 beta -estradiol-driven pathways involved in vessel assembly. We show that estrogens induce MCF7 breast cancer cells to secrete TGF beta 1. In addition, TGF beta cross talks with EGFR signaling pathway with concomitant up-regulation of EGFR ligand, TGF alpha, promoting cord-like formations in HUVEC cultures. The action of 17 beta -estradiol was not restricted to endothelium, since 17 beta -estradiol also stimulated recovery and migration of a smooth muscle cell line (FLTR) to injured areas again by the cross talk between these two signaling pathways. Finally, given the relevant role of 17 beta -estradiol in vessel stabilization, co-cultures of HUVEC and FLTR cells were established in the presence of 17 beta -estradiol or TGF beta 1. By blocking TGF beta or EGFR signaling, we demonstrate that 17 beta -estradiol promoted vessel stabilization through the interplay of TGF beta 1 and EGFR signaling transduction pathways. Our data suggest that estrogen mediates endothelial cell stabilization and vessel assembly. These vessel protective effects involve TGF beta 1 and EGFR signaling transduction pathways.

Adrenal Medulla↗
PubMed2002

Evaluation of breast cancer metastases in pleural effusions by molecular biology techniques.

The aim of this study was to evaluate the presence of allelic loss in chromosomal regions previously described as exhibiting loss of heterozygosity (LOH) during breast carcinogenesis, in pleural effusions of breast cancer patients. LOH was analyzed in three loci (1p32, 7q31, and 17q21). We studied 41 samples of pleural effusions from breast cancer patients (24 positive for neoplastic cells, 14 suspected, and 3 negative cases) and breast tissues from the patients (primary tumors and nonneoplastic adjacent tissue). DNA was extracted from pleural effusions, primary tumor, and adjacent normal tissue. LOH was evaluated by polymerase chain reaction assay and was observed in 38% of pleural effusions positive for neoplastic cells, and in 36% of suspected cases where morphology only did not allow the diagnosis of malignancy. We conclude that LOH analysis in pleural effusions of breast cancer patients is able to identify metastases in cases where morphologic analysis becomes difficult.

Breast Neoplasms↗
PubMed2000

Expression of TGF-alpha and EGFR in Breast Cancer and its Relation to Angiogenesis.

Immunohistochemical analysis of the expression of transforming growth factor alpha (TGF-alpha) and its receptor, epidermal growth factor receptor (EGFR), was performed in a series of 86 invasive carcinomas of the breast. TGF-alpha immunostaining was observed in the majority of the cases (72.1%), both in epithelial cells and in adjacent stromal cells. EGFR was also present in tumors (34.2%) and in the endothelial cells (46.1% of the cases) near the tumors. A significant association was observed between TGF-alpha expression and angiogenesis evaluated by immunohistochemistry using an antibody against factor VIII-related antigen. No association was observed between TGF-alpha expression and other clinicopathologic features. In contrast, EGFR expression in the tumor was associated with features of poor prognosis, such as tumor size, histologic grade, lymph node status, estrogen receptor content, p53 expression, sialyl-Tn expression, and age. The presence of EGFR in endothelial cells was correlated to young patient age. We also observed an association of EGFR in endothelial cells and angiogenesis in tumors with a size of less than 2 cm. Inversely, in larger tumors, angiogenesis was only associated with tumor TGF-alpha expression. These results indicate that endothelial EGFR may play a role in the early steps of breast cancer angiogenesis.

Journal Article↗
PubMedDate not supplied

Role of the estrogen antagonist ICI 182,780 in vessel assembly and apoptosis of endothelial cells.

Angiogenesis is required during tumor progression. Emerging data, including the presence of estrogen receptors in endothelium, suggests that estrogens can mediate endothelial proliferation and differentiation. Therefore, it is likely that anti-estrogenic drugs can also exert their effects in endothelial cells. The purpose of this work was to evaluate the effect of one anti-estrogenic agent, ICI 182,780, in human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs with 5 different concentrations of ICI 182,780 resulted in decreased cell viability and increase in apoptosis. Gene expression profile of these ICI-treated cells evaluated by cDNA array presented an upregulation of 68 newly expressed genes, whose expression was absent from both control and 17beta-estradiol-treated HUVECs. Most of these genes were implicated in both intrinsic and extrinsic apoptotic pathways. Furthermore, ICI 182,780 incubation prevented HUVECs from formity capillary-like tubules in a Matrigel assay. These findings suggest that besides blocking tumor cell proliferation in an estrogen receptor-dependent manner, ICI 182,780 impaired angiogenesis by preventing branching and capillary-like tubule formation and by activating apoptotic pathways in endothelial cells.

Apoptosis↗
PubMedDate not supplied

Angiogenesis: now and then.

Angiogenesis or new blood vessel formation plays an essential role during embryogenesis, adult vascular remodeling and in several pathological disorders, as in tumor development. Although sprouting of blood vessels is the principal angiogenic mechanism, additional ones, such as the recruitment of bone marrow-derived cells, have recently been described. These processes are controlled by several molecules, although members of the VEGF family of angiogenic factors and its receptors seem to be the main mediators. Initially, VEGF receptors were described as endothelial specific; however, further studies have reported their presence in several types of cells of non-endothelial origin, such as tumor cells. This VEGF receptor altered expression has suggested an angiogenesis-independent growth advantage mechanism on certain types of cancers by the generation of autocrine loops. A possible role in tumorigenesis and a potential novel target in cancer therapy have been hypothesized. Detection of other receptors and molecules considered to be angiogenic players has also been observed on tumor cells. Currently, their clinical significance as well as their potential as therapeutic targets for the treatment of certain cancers is being evaluated, having in mind the future development of promising mechanism-based therapies. The aspects mentioned above are the main focus of this review, which aims to throw light on recent findings respecting angiogenesis and novel therapeutic approaches.

Animals↗