Author:
Goo Young Ah,Goodlett David R,Pascal Laura E,Worthington Kelsey D,Vessella Robert L,True Lawrence D,Liu Alvin Y
Abstract
Abstract
Background
Stromal mesenchyme cells play an important role in epithelial differentiation and likely in cancer as well. Induction of epithelial differentiation is organ-specific, and the genes responsible could be identified through a comparative genomic analysis of the stromal cells from two different organs. These genes might be aberrantly expressed in cancer since cancer could be viewed as due to a defect in stromal signaling. We propose to identify the prostate stromal genes by analysis of differentially expressed genes between prostate and bladder stromal cells, and to examine their expression in prostate cancer.
Methods
Immunohistochemistry using antibodies to cluster designation (CD) cell surface antigens was first used to characterize the stromas of the prostate and bladder. Stromal cells were prepared from either prostate or bladder tissue for cell culture. RNA was isolated from the cultured cells and analyzed by DNA microarrays. Expression of candidate genes in normal prostate and prostate cancer was examined by RT-PCR.
Results
The bladder stroma was phenotypically different from that of the prostate. Most notable was the presence of a layer of CD13+ cells adjacent to the urothelium. This structural feature was also seen in the mouse bladder. The prostate stroma was uniformly CD13-. A number of differentially expressed genes between prostate and bladder stromal cells were identified. One prostate gene, proenkephalin (PENK), was of interest because it encodes a hormone. Secreted proteins such as hormones and bioactive peptides are known to mediate cell-cell signaling. Prostate stromal expression of PENK was verified by an antibody raised against a PENK peptide, by RT-PCR analysis of laser-capture microdissected stromal cells, and by database analysis. Gene expression analysis showed that PENK expression was down-regulated in prostate cancer.
Conclusion
Our findings show that the histologically similar stromas of the prostate and bladder are phenotypically different, and express organ-specific genes. The importance of these genes in epithelial development is suggested by their abnormal expression in cancer. Among the candidates is the hormone PENK and the down-regulation of PENK expression in cancer suggests a possible association with cancer development.
Publisher
Springer Science and Business Media LLC
Subject
Urology,Reproductive Medicine,General Medicine
Reference22 articles.
1. Cunha GR, Alarid ET, Turner T, Donjacour AA, Boutin EL, Foster BA: Normal and abnormal development of the male urogenital tract. Role of androgen, mesenchymal-epithelial interactions, and growth factors. J Androl. 1992, 13: 465-475.
2. Aboseif S, El-Sakka A, Young P, Cunha GR: Mesenchymal reprogramming of adult human epithelial differentiation. Differentiation. 1999, 65: 113-118. 10.1046/j.1432-0436.1999.6520113.x.
3. Bissell MJ, Ram TG: Regulation of functional cytodifferentiation and histogenesis in mammary epithelial cells: role of the extracellular matrix. Environ Health Persp. 1989, 80: 61-70.
4. Lee C: Role of androgen in prostate growth and regression: stromal-epithelial interaction. Prostate. 1996, 52-56. 10.1002/(SICI)1097-0045(1996)6+<52::AID-PROS10>3.0.CO;2-Q. suppl 6
5. Kedinger M, Lefebvre O, Duluc I, Freund JN, Simon-Assmann P: Cellular and molecular partners involved in gut morphogenesis and differentiation. Phil Trans R Soc Lond B Biol Sci. 1998, 353: 847-856. 10.1098/rstb.1998.0249.
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