Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer: a basis for tumor-promoting interactions.

The chemokines RANTES (CCL5) and MCP-1 (CCL2) were suggested to contribute, independently, to breast malignancy. In the present study, we asked if the two chemokines are jointly expressed in clinical samples of breast cancer patients, and do they interact in breast tumor cells. We found that RANTES and MCP-1 were expressed by breast tumor cells in primary tumors of Ductal Carcinoma In Situ and of Invasive Ductal Carcinoma, but minimally in normal breast epithelial duct cells.

Human endogenous retrovirus (HERV-K) reverse transcriptase as a breast cancer prognostic marker.

A reverse transcriptase (RT) cDNA, designated HERV-K-T47D-RT, was isolated from a hormonally treated human breast cancer cell line. The protein product putative sequence is 97% identical to the human endogenous HERV-K retroviral sequences. Recombinant T47D-RT protein was used to generate polyclonal antibodies.

Antibody internalization studied using a novel IgG binding toxin fusion.

Targeted therapy encompasses a wide variety of different strategies, which can be divided into direct or indirect approaches. Direct approaches target tumor-associated antigens by monoclonal antibodies (mAbs) binding to the relevant antigens or by small-molecule drugs that interfere with these proteins. Indirect approaches rely on tumor-associated antigens expressed on the cell surface with antibody-drug conjugates or antibody-based fusion proteins containing different kinds of effector molecules.

MUC1 gene overexpressed in breast cancer: structure and transcriptional activity of the MUC1 promoter and role of estrogen receptor alpha (ERalpha) in regulation of the MUC1 gene expression.

Background: The MUC1 gene encodes a mucin glycoprotein(s) which is basally expressed in most epithelial cells. In breast adenocarcinoma and a variety of epithelial tumors its transcription is dramatically upregulated. Of particular relevance to breast cancer, steroid hormones also stimulate the expression of the MUC1 gene.

The chemokine CCL5 as a potential prognostic factor predicting disease progression in stage II breast cancer patients.

Purpose: The aim of this study was to determine the prognostic value of the chemokine CCL5, considered as a promalignancy factor in breast cancer, in predicting breast cancer progression and to evaluate its ability to strengthen the prognostic significance of other biomarkers.

Experimental Design: The expression of CCL5, alone and in conjunction with estrogen receptor (ER)-alpha, ER-beta, progesterone receptor (PR), and HER-2/neu (ErbB2), was determined in breast tumor cells by immunohistochemistry. The study included 142 breast cancer patients, including individuals in whom disease has progressed.

A novel protein derived from the MUC1 gene by alternative splicing and frameshifting.

Genes that have been designated the name "MUC" code for proteins comprising mucin domains. These proteins may be involved in barrier and protective functions. The first such gene to be characterized and sequenced is the MUC1 gene.

The angiogenic factors CXCL8 and VEGF in breast cancer: regulation by an array of pro-malignancy factors.

The regulation of secretion of the angiogenic factors CXCL8 and Vascular Endothelial Growth Factors (VEGF) was determined in breast tumor cells and in monocytic cells (as host cells that contribute to breast cancer). CXCL8 secretion, and partly the secretion of VEGF, were up-regulated in monocytic cells, but not in breast tumor cells, by the CC chemokines CCL5 and CCL2. EGF potently up-regulated CXCL8 secretion by breast tumor cells, and its effect was promoted by a consecutive treatment of the cells by estrogen and progesterone.

A unique mucin immunoenhancing peptide with antitumor properties.

Implantation of DA-3 mammary tumor cells into BALB/c mice results in tumor growth, metastatic lesions, and death. These cells were transfected with genes encoding for either the transmembrane (DA-3/TM) or secreted (DA-3/sec) form of human mucin 1 (MUC1). Although the gene for the secreted form lacks the transmembrane and cytoplasmic domains, the 5' sequences of these mucins are identical; however, the gene for the secreted mucin isoform ends with a sequence encoding for a unique 11 amino acid peptide.

Humanization and epitope mapping of the H23 anti-MUC1 monoclonal antibody reveals a dual epitope specificity.

The tumor-associated antigen MUC1 is a cell surface mucin that is expressed on the apical surface of most glandular epithelial cells, including the ducts of the breast, ovary, pancrease, lung and colon. During malignancy, epithelial tissues regularly display elevated levels of MUC1 in a non-polar fashion and in an underglycosylated form, exposing cryptic peptide and carbohydrate epitopes. As such, MUC1 is regarded a potential target for immunotherapeutical intervention.

Breast carcinoma: a report on the potential usage of the CC chemokine RANTES as a marker for a progressive disease.

Background: High incidence and intensity of RANTES (CC chemokine) expression were noted in advanced breast carcinoma.

Objective: To present two cases of breast carcinoma patients in whom RANTES expression was analyzed in parallel to disease progression.

Results: Although no evidence of malignancy was detected in the axillary lymph nodes of the two patients, their disease progressed.

The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity.

Breast cancer progression may be affected by various cellular components expressed by the tumor cells and/or by microenvironmental factors. Many studies report the correlation between breast cancer progression and monocyte infiltration into the tumor site. We have identified recently the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES), a major monocyte chemoattractant expressed by breast tumor cells, as a potential contributor to breast cancer progression.

Generation of ligand-receptor alliances by "SEA" module-mediated cleavage of membrane-associated mucin proteins.

A mechanism is described whereby one and the same gene can encode both a receptor protein as well as its specific ligand. Generation of this receptor-ligand partnership is effected by proteolytic cleavage within a specific module located in a membrane resident protein. It is postulated here that the "SEA" module, found in a number of heavily O-linked glycosylated membrane-associated proteins, serves as a site for proteolytic cleavage.