Transcriptional profiling of inductive mesenchyme to identify molecules involved in prostate development and disease

The mesenchymal compartment plays a key role in organogenesis, and cells within the mesenchyme/stroma are a source of potent molecules that control epithelia during development and tumorigenesis. We used serial analysis of gene expression (SAGE) to profile a key subset of prostatic mesenchyme that regulates prostate development and is enriched for growth-regulatory molecules.

SAGE libraries were constructed from prostatic inductive mesenchyme and from the complete prostatic rudiment (including inductive mesenchyme, epithelium, and smooth muscle). By comparing these two SAGE libraries, we generated a list of 219 transcripts that were enriched or specific to inductive mesenchyme and that may act as mesenchymal regulators of organogenesis and tumorigenesis. We identified Scube1 as enriched in inductive mesenchyme from the list of 219 transcripts; also, quantitative RT-PCR and whole-mount in situ hybridization revealed Scube1 to exhibit a highly restricted expression pattern. The expression of Scube1 in a subset of mesenchymal cells suggests a role in prostatic induction and branching morphogenesis. Additionally, Scube1 transcripts were expressed in prostate cancer stromal cells, and were less abundant in cancer associated fibroblasts relative to matched normal prostate fibroblasts.

The use of a precisely defined subset of cells and a back-comparison approach allowed us to identify rare mRNAs that could be overlooked using other approaches. We propose that Scube1 encodes a novel stromal molecule that is involved in prostate development and tumorigenesis.