Dickkopf-1 (Dkk1) protein expression in breast cancer with special reference to bone metastases
Dysregulation of the Wnt inhibitor dickkopf-1 protein (Dkk1) has been reported in a variety of cancers. In addition, it has been linked to the progression of malignant bone disease by impairing osteoblast activity. This study investigated serum- and tissue levels of Dkk1 in breast cancer patients with- or without bone metastases. Serum Dkk1 levels were measured by ELISA in 89 breast cancer patients and 86 healthy women. Tissue levels of Dkk1 and β-catenin, a major downstream component of Wnt transduction pathway, were tested with immunohistochemical staining in 143 different tissues, including adjacent non-tumoral breast tissues, primary breast tumours, lymph nodes metastases, and bone metastases. Serum levels of Dkk1 were significantly increased in breast cancer patients without metastases compared with healthy controls and even more increased in patients with bone metastases. Tissue expression of Dkk1 was positive in 70% of tested primary breast cancer tissues and demonstrated significant correlation with histological type and PR status. Less frequent expression of Dkk1 was found in lymph nodes metastases and bone metastases compared with adjacent non-tumoral breast tissues and primary breast tumours. Tissue expression of β-catenin was positive in the vast majority of all tested tissue types indicating activated Wnt/β-catenin signalling. Our results suggested that Wnt/β-catenin signalling in breast tumours and their secondary lymph nodes- and bone metastases is dysregulated and this could be related to aberrant Dkk1 expression levels. Hence, Dkk1 protein might provide insights into the continued development of novel comprehensive and therapeutic strategies for breast cancer and its bone metastases.
KeywordsBreast cancer Dickkopf-1 (Dkk1) Bone metastases β-Catenin Target therapy
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This study was approved by the local Ethic Committee of the Medical Association of the Saarland (Reference Number: 09/14). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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