Igf1r is not required for AIB1-induced mammary hyperplasia and ductal branching

• Published in: Frontiers in bioscience (Elite edition) Vol. 4; no. 7; p. 2536
• Main Authors: Senoret, Vanesa, Orlando, Leonardo, Brunning, Jens, Font de Mora, Jaime
• Format: Journal Article
• Language: English
• Published: Singapore 01.06.2012
• Subjects: Animals; Base Sequence; Blotting, Western; Cells, Cultured; DNA Primers; Female; Hyperplasia; Immunohistochemistry; Mammary Glands, Animal - pathology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Polymerase Chain Reaction; Receptor, IGF Type 1 - physiology
• ISSN: 1945-0508
• DOI: 10.2741/e564

The oncogene AIB1 (amplified in breast cancer 1) is a transcriptional coactivator which is up-regulated in many types of tumors including breast cancer. Studies with cell lines and animal models reveal that AIB1 interacts with the IGF-I signaling pathway at different molecular levels. To determine whether AIB1-dependent cell growth requires IGF-I signaling, we deleted the Igf1r gene specifically in the mammary gland of transgenic mice which overexpress AIB1 and are characterized by the development of epithelial hyperplasia, a pre-neoplastic change in breast tissue. Loss of Igf1r alone reduced cell proliferation, ductal branching and fat pad occupancy in comparison with wild-type glands. However, in the transgenic mice that overexpress moderate levels of AIB1, the absence of Igf1r had a minimal effect on epithelial hyperplasia and ductal branching in the mammary gland. Thus, our results confirm the essential role of Igf1r in mammary gland morphogenesis and demonstrate that overexpression of AIB1 circumvents the requirement for the Igf1r pathway in promoting epithelial growth during mammary development.