Specific protection against breast cancers by cyclin D1 ablation.
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.
Yu
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Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Geng
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Y
Sicinski
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P
D000818:Animals; D030801:Animals, Genetically Modified; D000970:Antineoplastic Agents / Q000494:pharmacology; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D003433:Crosses, Genetic; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D005260:Female; D019940:Genes, bcl-1; D018734:Genes, erbB-2; D016259:Genes, myc; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism; D008324:Mammary Tumor Virus, Mouse; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; D019938:Cyclin D1