Specific protection against breast cancers by cyclin D1 ablation

• Published in: Nature (London) Vol. 411; no. 6841; pp. 1017 - 1021
• Main Authors: Sicinski, Piotr, Yu, Qunyan, Geng, Yan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 28.06.2001; Nature Publishing Group
• Subjects: Animals; Animals, Genetically Modified; Antineoplastic Agents - pharmacology; Biological and medical sciences; Breast - metabolism; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; c-myc gene; Cell Transformation, Neoplastic; Crosses, Genetic; cyclin D1; Cyclin D1 - antagonists & inhibitors; Cyclin D1 - deficiency; Cyclin D1 - physiology; Female; Genes, bcl-1; Genes, erbB-2; Genes, myc; Genes, ras; Genetic Predisposition to Disease; Genetics; Gynecology. Andrology. Obstetrics; Humans; Male; Mammary gland diseases; Mammary Neoplasms, Experimental - genetics; Mammary Neoplasms, Experimental - metabolism; Mammary Tumor Virus, Mouse; Medical sciences; Mice; Molecular biology; Neu protein; Proteins; Proto-Oncogene Proteins - genetics; Rodents; Tumor Cells, Cultured; Tumors; Wnt Proteins; Wnt1 Protein; Zebrafish Proteins; Rodentia; Malignant tumor; Cyclin D1; Carcinogenesis; Mammary gland diseases; Vertebrata; Mammalia; Mouse; Animal; C-Onc gene; Genetics; Mammary gland; Protooncogene
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35082500

Breast cancer is the most common malignancy among women. Most of these cancers overexpress cyclin D1, a component of the core cell-cycle machinery. We previously generated mice lacking cyclin D1 using gene targeting. Here we report that these cyclin D1-deficient mice are resistant to breast cancers induced by the neu and ras oncogenes. However, animals lacking cyclin D1 remain fully sensitive to other oncogenic pathways of the mammary epithelium, such as those driven by c-myc or Wnt-1. Our analyses revealed that, in mammary epithelial cells, the Neu-Ras pathway is connected to the cell-cycle machinery by cyclin D1, explaining the absolute dependency on cyclin D1 for malignant transformation in this tissue. Our results suggest that an anti-cyclin D1 therapy might be highly specific in treating human breast cancers with activated Neu-Ras pathways.