title: Elevated p-CREB-2 (ser 245) expression is potentially associated with             carcinogenesis and development of breast carcinoma.
abstract: 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.
authors: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang 110001, PR China.
authors: Chui-Feng
authors: CF
authors: Fan
authors: Xiao-Yun
authors: XY
authors: Mao
authors: En-Hua
authors: EH
authors: Wang
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D005260:Female; D005348:Fibrocystic Breast Disease / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: C497109:ATF4 protein, human; D051701:Activating Transcription Factor 4; D012694:Serine