The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types

Abstract

In addition to new tumour antigens, new prognostic and diagnostic markers are needed for common cancers. In this study, we report the expression of Dickkopf-1 (DKK1) in multiple common cancers. This constitutes a comprehensive analysis of the DKK1 expression profile. Dickkopf-1 expression was evaluated by classical and quantitative reverse transcriptase -polymerase chain reaction (RT -PCR) and enzyme-linked immunosorbant assay for protein determination, in cancer lines and clinical specimens of several cancer origins. For breast cancer, expression was correlated with clinicopathological parameters. Dickkopf-1 expression was confirmed in several cancer cell lines derived from breast and other common cancers. Dickkopf-1 protein secretion was documented in breast, prostate and lung cancer lines, but was negligible in melanoma. Analysis of DKK1 expression in human cancer specimens revealed DKK1 expression in breast (21 out of 73), lung (11 out of 23) and kidney cancers (six out of 20). Interestingly, DKK1 was preferentially expressed in oestrogen and progesterone receptor-negative tumours (ER À /PR À ; P ¼ 0.005) and in tumours from women with a family history of breast cancer (P ¼ 0.024). Importantly, DKK1 protein production was confirmed in multiple breast cancer specimens that were positive by RT -PCR. This work establishes DKK1 as a potential prognostic and diagnostic marker for cohorts of breast cancer patients with poor prognosis. Dickkopf-1 may also become a relevant candidate target for immunotherapy of different cancers.

Plasma and vitreous fluid levels of Dickkopf-1 in patients with diabetic retinopathy

“…21 This result was supported by our data in this study that DKK-1 was at low levels (18.69-239.52 pg/ml) in human vitreous, being strikingly lower than those in the plasma in controls. Our result suggests that DKK-1 may be produced at low levels in ocular tissues, and little of the circulating DKK-1 may leak into the ocular fluid under normal conditions.…”

A potential role for Dkk-1 in the pathogenesis of osteosarcoma predicts novel diagnostic and treatment strategies

“…Assays of Dkk-1 secretion could therefore represent a useful diagnostic and prognostic tool for the evaluation of OS patients. Dkk-1 is also upregulated by other malignant cell lines (Wirths et al, 2003;Forget et al, 2007), suggesting that serum Dkk-1 measurements may be useful for the evaluation of other types of malignancy, but the significance of Dkk-1 expression is not presently clear in tumours that do not affect bone. Although the data presented here demonstrate that Dkk-1 may contribute to OS pathogenesis by preventing repair of the surrounding osteoid as the tumour expands, Dkk-1 may act in an autocrine manner on the tumour cells too.…”

Dysregulation of Wnt Signaling in Breast Cancer

“…Furthermore, as mentioned above, aberrant Wnt/β-catenin signaling is involved in breast cancer development and progression. Indeed, Dkk1 is highly expressed in several breast cancer cell lines, including the MDA-MB-231 (osteolytic) and MCF-7 (osteolytic and osteoblastic) cell lines (Forget et al, 2007;Pinzone et al, 2009;Bu et al, 2008). Additionally, serum Dkk1 levels were elevated in patients with metastasized breast cancer in the bone compared to patients who were in complete remission (Voorzanger-Rousselot et al, 2007).…”