WNT5-ALPHA CLONING, EXPRESSION, AND UP-REGULATION IN HUMAN PRIMARY BREAST CANCERS

Wnt genes are involved in mouse mammary cancer, but their role in huma n cancer is unknown, Human Wnt5a was cloned from a placental cDNA libr ary and used to assess expression by ribonuclease protection and in si tu hybridization in human breast cell lines and in normal, benign, and malignant breast tissues, Human Wnt5a shows over 99% homology at amin o acid level with mouse Wnt5a, and 90% with Xenopus Wnt5a, It was expr essed only at low levels in breast cell lines and normal breast tissue , Benign proliferations and invasive cancer respectively showed 10-fol d and 4-fold higher Wnt5a than normal breast tissues, The greater up-r egulation in benign conditions suggests a role in aberrant differentia tion. In situ hybridization localized the signal to the epithelial com ponent, Wnt5a is the first member of the Wnt family to demonstrate ove rexpression in human breast cancer, It was not associated with factors known to affect breast cancer prognosis such as lymph node status or epidermal growth factor receptor status.