Development of Normal Prostate

Authors
C Butler, A Swain
Institute of Cancer Research
Source of funding: NCRI

Developmental Genetics of the Prostate
Given that carcinogenesis often involves deregulation of developmental regulatory genes, a molecular analysis of normal development of the prostate should provide important insight into prostate cancer. Although the androgen-dependent nature of prostate development has been well established, it is not clear how androgens regulate prostate differentiation and growth. Identification of the gene pathways regulated by androgens during prostate development is essential for the understanding of normal and disease processes of this male-specific organ. The use of high-density cDNA hybridisation arrays and subtractive hybridisation techniques can identify these gene pathways. These can be further studied by transgenic analysis in mouse models.
In a collaboration with Dr. Bento Soares (University of Iowa) we have developed a normalised cDNA library derived from neonatal mouse prostate. We are screening this library to identify overexpressed clones in the developing male prostate compared to female tissues. Genes of interest will be sequenced and their expression characterised by whole-mount in situ hybridisation and subjected to functional analysis using in vitro organ cultures, transgenic and/or targeted mutagenesis in the mouse. Genes identified in this project may provide useful prognostic markers for early prostate cancer.

Urogenital system of the mouse	Developing epithelial buds of the prostate - marked by the gene Nkx3.1	Expression of E-cadherin in the developing seminal vesicles