|Up-regulation and overproduction of DVL-1, the human counterpart of the Drosophila dishevelled gene, in cervical squamous cell carcinoma|
Authors: Keiko Okino, Hisaki Nagai, Mitsuko Hatta, Takemitsu Nagahata, Koichi Yoneyama, Yujiro Ohta, Enjing Jin, Oichi Kawanami, Tsutomu Araki, Mitsuru Emi
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kosugi, Kawasaki 211-8533, Japan
The Dvl-1 gene on chromosome 1p36 belongs to a family of highly conserved secreted proteins which regulates embryonic induction, generation of cell polarity and specification of cell fate through activation of Wnt signaling pathways. Wnt signaling activates the gene encoding DVL-1; the latter suppresses β-catenin by promoting its degradation through enhanced inactivation of glycogen-synthase-kinase 3 (GSK3). Here we demonstrate increased expression of DVL-1 mRNA in over two thirds of primary cervical squamous cell cancers (11 of 15 cases) when compared to corresponding non-cancerous uterine squamous cell tissues. In addition, we noted up-regulation of cyclin D1, a downstream effector of Wnt signal pathway in cervical cancer. Immunohistochemical staining demonstrated that DVL-1 protein was prominent in the cytoplasm of cancer cells whereas it was unreactive in the surrounding normal cervical squamous cells. These data indicate that amplification and increased expression of the DVL-1 gene may play some role in the development of a portion of human cervical squamous cell cancer through derangement of the Wnt signaling pathway.