A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer.

Elevated expression of the chemokine receptor CCR4 in tumors is associated with poor prognosis in several cancers. Here, we have determined that CCR4 was highly expressed in human renal cell carcinoma (RCC) biopsies and observed abnormal levels of CCR4 ligands in RCC patient plasma. An antagonistic anti-CCR4 antibody had antitumor activity in the RENCA mouse model of RCC.

Integrated transcriptomic and proteomic analysis identifies protein kinase CK2 as a key signaling node in an inflammatory cytokine network in ovarian cancer cells.

We previously showed how key pathways in cancer-related inflammation and Notch signaling are part of an autocrine malignant cell network in ovarian cancer. This network, which we named the "TNF network", has paracrine actions within the tumor microenvironment, influencing angiogenesis and the immune cell infiltrate.The aim of this study was to identify critical regulators in the signaling pathways of the TNF network in ovarian cancer cells that might be therapeutic targets.

Alternative TFAP2A isoforms have distinct activities in breast cancer.

Introduction: AP-2α is a transcription factor implicated in the regulation of differentiation and proliferation in certain tissues, including the mammary gland. In breast tumours, continued expression of AP-2α has been correlated with a better prognosis, but this is hard to reconcile with a reported role in the upregulation of the ERBB2 oncogene. The existence of TFAP2A isoforms, deriving from alternative first exons and differing in their N-terminal sequence, has been described in some mammals, but their relative abundance and activity has not been investigated in the human breast.

Dual association by TFAP2A during activation of the p21cip/CDKN1A promoter.

The cyclin-dependent kinase inhibitor p21cip/CDKN1A is induced to promote growth arrest in response to a variety of stimuli in normal cells and loss of correct regulation of this gene is frequently observed in cancer. In particular, the upregulation of CDKN1A by p53 is considered to be a central mechanism of tumour suppression. Other transcription factors with tumour suppressor activity can also regulate CDKN1A, including the developmentally regulated factor, TFAP2A.

AP-2gamma promotes proliferation in breast tumour cells by direct repression of the CDKN1A gene.

Overexpression of the activator protein (AP)-2gamma transcription factor in breast tumours has been identified as an independent predictor of poor outcome and failure of hormone therapy. To understand further the function of AP-2gamma in breast carcinoma, we have used an RNA interference and gene expression profiling strategy with the MCF-7 cell line as a model. Gene expression changes between control and silenced cells implicate AP-2gamma in the control of cell cycle progression and developmental signalling.