Poster Presentation 25th Lorne Cancer Conference 2013

Deletion of Myb in keratin 14 expressing cells delays mammary cancer onset (#150)

Ryan Cross 1 , Shienny Sampurno 1 , Rebecca Miao 1 , Robin Anderson 1 , Robert Ramsay 1
  1. Research, Peter MacCallum Cancer Centre, Melbourne East, Vic, Australia

Transcription factors that regulate proliferation and differentiation have long been associated with cancer. Their deregulation allows tumour cells to acquire many features of stem and progenitor cells, such as proliferation and suppression of differentiation. MYB is a transcription factor involved in the development and maintenance of stem cell niches of various epithelial tissues and their associated cancers. Until recently, its direct involvement in breast cancer has not been investigated. Here we explore its function in the developing mammary gland and in tumour initiation using conditional knock-out and spontaneous tumourigenesis mouse models. By utilising a Keratin 14-Cre mouse crossed to a c-mybf/f mouse, we are able to delete c-Myb in K14 expressing epithelial cells. The loss of c-Myb transcriptional activity decreases the proliferative potential of both the luminal and basal cells of the mammary gland, whilst ultimately allowing a functional gland to develop. Crossing the K14Cre/c-mybf/f mouse to the MMTV-PyMT mouse, that develops aggressive mammary tumours, leads to a significant delay in tumour onset. From our study we conclude that c-Myb is required for the maintenance of a complete stem and progenitor pool within the mammary gland and that, loss of c-Myb decreases potential targets of tumourigenesis in the MMTV-PyMT mouse.