Wnt5a cloning, expression, and up-regulation in human primary breast cancers

• Published in: Clinical cancer research Vol. 1; no. 2; pp. 215 - 222
• Main Authors: LEJEUNE, S, HUGUET, E. L, HAMBY, A, POULSOM, R, HARRIS, A. L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.02.1995
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Brain - metabolism; Breast - cytology; Breast - metabolism; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Chromosome Mapping; Chromosomes, Human, Pair 3; Cloning, Molecular; Conserved Sequence; Female; Fetus; Gene Library; Gynecology. Andrology. Obstetrics; Humans; In Situ Hybridization; Mammary gland diseases; Medical sciences; Mice; Molecular Sequence Data; Neoplasm Invasiveness; Neoplasm Staging; Placenta - metabolism; Pregnancy; Proteins - chemistry; Proteins - genetics; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins - genetics; Recombinant Proteins - biosynthesis; Recombinant Proteins - chemistry; Tumor Cells, Cultured; Tumors; Wnt Proteins; Wnt-5a Protein; Xenopus; Xenopus Proteins; Human; Mammary gland diseases; Pathogenesis; Established cell line; Gene overexpression; Mammary gland; Malignant tumor; Molecular cloning; Gene expression; Onc gene; In vitro
• ISSN: 1078-0432; 1557-3265

Wnt genes are involved in mouse mammary cancer, but their role in human cancer is unknown. Human Wnt5a was cloned from a placental cDNA library and used to assess expression by ribonuclease protection and in situ hybridization in human breast cell lines and in normal, benign, and malignant breast tissues. Human Wnt5a shows over 99% homology at amino acid level with mouse Wnt5a, and 90% with Xenopus Wnt5a. It was expressed only at low levels in breast cell lines and normal breast tissue. Benign proliferations and invasive cancer respectively showed 10-fold and 4-fold higher Wnt5a than normal breast tissues. The greater up-regulation in benign conditions suggests a role in aberrant differentiation. In situ hybridization localized the signal to the epithelial component. Wnt5a is the first member of the Wnt family to demonstrate overexpression 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.