Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848576 (breast hyperplasia)
 35 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CREB-2, also known as ATF-4, belongs to the CREB proteins, a family of transcription factors phosphorylated at serine residues by protein kinase A (PKA). This family is known to stimulate the transcription of genes containing CRE elements. Recently, some studies have demonstrated elevated CREB-2 expression in certain tumor types, including breast carcinoma, compared to their corresponding non-tumor tissues. However, the expression and clinical significance in malignant tumors, including breast carcinoma, of p-CREB-2 (ser 245), a phosphorylated form of the CREB-2 protein at serine 245 site, which is believed to be an active type of this protein, have not been clearly documented. In the present study, we investigated the expression of p-CREB-2 (ser 245) in a group of tumor and non-tumor breast tissues, including normal breast epithelia, hyperplasia, dysplasia, carcinoma in situ and infiltrating carcinoma of the breast using tissue microarray and immunohistochemistry (IHC). p-CREB-2 (ser 245) immunostaining was detected in the nucleus and cytoplasm of these tissues. Compared to normal breast epithelia and breast hyperplasia (total positive rate 13.3%), there was increased expression of p-CREB-2 (ser 245) in dysplasia, carcinoma in situ (total positive rate 35.7%) and infiltrating carcinoma of the breast (total positive rate 60.0%) (p<0.05). The highest expression of p-CREB-2 (ser 245) was found in infiltrating breast carcinoma (total positive rate 60%) compared to normal breast epithelia and all types of non-infiltrating lesions (total positive rate 27.6%) (p<0.05). In addition, increased expression of p-CREB-2 (ser 245) was found to be associated with lymph node metastasis in infiltrating breast carcinoma (p<0.05). Immunofluorescent staining confirmed stronger staining of p-CREB-2 (ser 245) in breast cancer MCF 7 and MDA-MB-231 cells compared with normal breast epithelial MCF 10A cells. Western blotting revealed elevated expression levels of p-CREB-2 (ser 245) in 17 cases of breast carcinoma compared with corresponding normal breast tissues (p<0.05). These results indicate that elevated expression of p-CREB-2 (ser 245) may potentially contribute to carcinogenesis and cancer development of breast carcinoma.
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PMID:Elevated p-CREB-2 (ser 245) expression is potentially associated with carcinogenesis and development of breast carcinoma. 2205 62

Natural compounds derived from plants have been an important source of numerous clinically useful anticancer agents. Nevertheless, limited studies indicate that xanthohumol (XN), a major prenylated flavonoid in hop plants (Humulus lupulus), may possess anticarcinogenic properties. The purpose of the present study was to clarify the antitumorigenic effects and the underlying mechanism of XN on breast cancer in vivo and in vitro. A 4T1 breast tumor mouse model was used in the present study to investigate XN suppression of tumor growth as detected by tumorigenicity assays in vivo. In addition, in vitro studies revealed that XN significantly decreased cell viability, induced G0/G1 cell cycle arrest and apoptosis in MCF-7 and MDA-MB-231 cells, as confirmed by an MTT assay, flow cytometry and western blot analysis, indicating anticarcinogenic activity of XN against breast cancer. Furthermore, immunohistochemistry was performed to confirm the inactivation of the Notch signaling pathway, Notch 1 and Ki-67, in vivo; consistently, XN caused decreased activation of the Notch signaling pathway and apoptotic regulators B-cell lymphoma-2 (Bcl-2), Bcl-extra large and caspase 3, as determined by western blot analysis in vitro. This study suggests that XN may potentially be useful as a chemopreventive agent during breast hyperplasia and carcinogenesis, acting via the regulation of Notch associated apoptotic regulators in vivo and in vitro.
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PMID:Inhibition of breast cancer cell survival by Xanthohumol via modulation of the Notch signaling pathway in vivo and in vitro. 2942 66