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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Predictive markers and variables for response to anticancer therapy provide cancer patients with refinement of therapeutic options and a decreased likelihood of receiving an ineffective therapy. The best-established predictive marker for response to endocrine therapy for breast cancer is the status of estrogen receptors (ER) in the primary breast tumor. However, although patients with ER-positive tumors have a greater than 50% objective response rate to endocrine therapy, other patients can not obtain an objective response. Therefore additional markers, such as better molecular biologic markers, are needed. Our previous study using multivariate analysis revealed that the ER status of primary tumors and the dominant site of metastasis are independent predictors for response to first-line endocrine therapy and that a response to first-line endocrine therapy is only an independent predictor for response to second-line endocrine therapy. However, all these factors are already well-established predictive markers for response to endocrine therapy. Recently, a number of new hormonal agents, such as more selective aromatase inhibitors and specific antiestrogens, have been developed and introduced. However, several questions, such as the best sequences when using hormonal agents, remain to be elucidated. On the other hand, several molecular biologic markers predicting response to endocrine therapy, such as the expression of the HER family of tyrosine kinase receptors, pS2, Bcl-2, and vascular endothelial growth factor, have been reported. To elucidate the most effective use of endocrine therapy for recurrent breast cancer, classical and new predictive factors for response to endocrine therapy are reviewed, and the clinical implications of these factors are discussed.
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PMID:Predictive factors for response to endocrine therapy in patients with recurrent breast cancer. 1111 53

In our study, we present experimental evidence suggesting that curcumin exerts multiple different suppressive effects on human breast carcinoma cells in vitro. Our experiments demonstrate that curcumin's antiproliferative effects are estrogen dependent in ER (estrogen receptor)-positive MCF-7 cells, being more pronounced in estrogen-containing media and in the presence of exogenous 17-beta estradiol. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF-beta (transforming growth factor) in ER-positive MCF-7 cells, and this inhibition is also dependent on the presence of estrogen. Curcumin also decreases ERE (estrogen responsive element)-CAT activities induced by 17-beta estradiol. In addition, we demonstrate that curcumin exerts strong anti-invasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive effects appear to be mediated through the downregulation of MMP-2 (matrix metalloproteinase) and the upregulation of TIMP-1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion. Our study also demonstrates that curcumin inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor) mainly in ER-negative MDA-MB-231 cells.
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PMID:Curcumin exerts multiple suppressive effects on human breast carcinoma cells. 1185 14

We previously established that the trefoil peptides (TFFs) pS2, spasmolytic polypeptide, and intestinal trefoil factor are involved in cellular scattering and invasion in kidney and colonic cancer cells. Using the chorioallantoic membrane (CAM) assay and the formation of tube-like structures by human umbilical vein endothelial cells (HUVEC) plated on the Matrigel matrix substratum, we report here that TFFs are proangiogenic factors. Angiogenic activity of TFFs is comparable to that induced by vascular endothelial growth factor, leptin, and transforming growth factor-alpha. Stimulation of angiogenesis by pS2 in the CAM assay is blocked by pharmacological inhibitors of cyclooxygenase COX-2 (NS-398) and epidermal growth factor receptor (EGF-R) tyrosine kinase (ZD1839), but is independent of KDR/Flk-1 and thromboxane A2 receptors. In contrast, the morphogenic switch induced by pS2 in HUVEC cells could be inhibited by the specific KDR heptapeptide antagonist ATWLPPR and by inhibitors of COX-2 and EGF-R signaling. These results implicate TFFs in the formation of new blood vessels during normal and pathophysiological processes linked to wound healing, inflammation, and cancer progression in the digestive mucosa and other human solid tumors associated with aberrant expression of TFFs.
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PMID:Trefoil peptides as proangiogenic factors in vivo and in vitro: implication of cyclooxygenase-2 and EGF receptor signaling. 1252 7

Signal transducer and activator of transcription (STAT) 3 is overexpressed or activated in most types of human tumors and has been classified as an oncogene. In the present study, we investigated the contribution of the STAT3s to the proinvasive activity of trefoil factors (TFF) and vascular endothelial growth factor (VEGF) in human colorectal cancer cells HCT8/S11 expressing VEGF receptors. Both intestinal trefoil peptide (TFF3) and VEGF, but not pS2 (TFF1), activate STAT3 signaling through Tyr(705) phosphorylation of both STAT3alpha and STAT3beta isoforms. Blockade of STAT3 signaling by STAT3beta, depletion of the STAT3alpha/beta isoforms by RNA interference, and pharmacologic inhibition of STAT3alpha/beta phosphorylation by cucurbitacin or STAT3 inhibitory peptide abrogates TFF- and VEGF-induced cellular invasion and reduces the growth of HCT8/S11 tumor xenografts in athymic mice. Differential gene expression analysis using DNA microarrays revealed that overexpression of STAT3beta down-regulates the VEGF receptors Flt-1, neuropilins 1 and 2, and the inhibitor of DNA binding/differentiation (Id-2) gene product involved in the neoplastic transformation. Taken together, our data suggest that TFF3 and the essential tumor angiogenesis regulator VEGF(165) exert potent proinvasive activity through STAT3 signaling in human colorectal cancer cells. We also validate new therapeutic strategies targeting STAT3 signaling by pharmacologic inhibitors and RNA interference for the treatment of colorectal cancer patients.
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PMID:Implication of STAT3 signaling in human colonic cancer cells during intestinal trefoil factor 3 (TFF3) -- and vascular endothelial growth factor-mediated cellular invasion and tumor growth. 1566 95

Royal jelly (RJ) from honeybees (Apis mellifera) is traditionally thought to improve menopausal symptoms. The potential estrogenic activities of RJ were investigated using various approaches. RJ competed for binding of 17beta-estradiol to the human estrogen receptor alpha and beta but its affinities were weak compared with diethylstilbestrol and phytoestrogens. The reporter gene expression assays suggested that 0.1-1 mg/ml RJ activated estrogen receptors, leading to enhanced transcription of a reporter gene through an estrogen-responsive element. 1 mg/ml RJ stimulated the mRNA expression of estrogen-responsive pS2 and vascular endothelial growth factor (VEGF) by increasing gene transcription in MCF-7 cells. Treatment with RJ at concentrations ranging from 0.5 to 1 mg/ml enhanced MCF-7 cell proliferation, but concomitant treatment with 1 microM tamoxifen blocked this effect. In vivo studies using ovariectomized rats showed that 17beta-estradiol (20 mg/kg, s.c.) treatment restored VEGF expression in both uterus and brain, whereas RJ (1 g/kg, s.c.) restored it in uterus but not in brain. These findings provide evidence that RJ has estrogenic activities through interaction with estrogen receptors followed by endogenous gene expressions.
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PMID:Royal jelly has estrogenic effects in vitro and in vivo. 1594 13

This study aimed to elucidate which component of flaxseed, i.e. secoisolariciresinol diglucoside (SDG) lignan or flaxseed oil (FO), makes tamoxifen (TAM) more effective in reducing growth of established estrogen receptor positive breast tumors (MCF-7) at low circulating estrogen levels, and potential mechanisms of action. In a 2 x 2 factorial design, ovariectomized athymic mice with established tumors were treated for 8 wk with TAM together with basal diet (control), or basal diet supplemented with SDG (1 g/kg diet), FO (38.5 g/kg diet), or combined SDG and FO. SDG and FO were at levels in 10% flaxseed diet. Palpable tumors were monitored and after animal sacrifice, analyzed for cell proliferation, apoptosis, ER-mediated (ER-alpha, ER-beta, trefoil factor 1, cyclin D1, progesterone receptor, AIBI), growth factor-mediated (epidermal growth factor receptor, human epidermal growth factor receptor-2, insulin-like growth factor receptor-1, phosphorylated mitogen activated protein kinase, PAKT, BCL2) signaling pathways and angiogenesis (vascular endothelial growth factor). All treatments reduced the growth of TAM-treated tumors by reducing cell proliferation, expression of genes, and proteins involved in the ER- and growth factor-mediated signaling pathways with FO having the greatest effect in increasing apoptosis compared with TAM treatment alone. SDG and FO reduced the growth of TAM-treated tumors but FO was more effective. The mechanisms involve both the ER- and growth factor-signaling pathways.
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PMID:Dietary flaxseed lignan or oil combined with tamoxifen treatment affects MCF-7 tumor growth through estrogen receptor- and growth factor-signaling pathways. 1990 59