Epithelial defect in prostates of Stat5a-null mice. Lab Invest 2000 Jul;80(7):993-1006
Date
07/25/2000Pubmed ID
10908145DOI
10.1038/labinvest.3780105Scopus ID
2-s2.0-0033914135 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
The transcription factor Stat5a critically mediates prolactin (PRL)-induced mammary gland development and lactogenesis. PRL also stimulates growth and differentiation of prostate tissue. Specifically, hyperprolactinemia gives rise to prostate hyperplasia, and prostate size is reduced in PRL-deficient mice. We therefore investigated the importance of Stat5a for prostate development and function by examining Stat5a-null mice. The absence of Stat5a in mice was associated with a distinct prostate morphology characterized by an increased prevalence of local disorganization within acinar epithelium of ventral prostates. Affected acini were typically filled with desquamated, granular epithelial cells that had become embedded in dense, coagulated secretory material. These features were reminiscent of acinar cyst formation and degeneration frequently observed in human benign prostate hyperplasia, however, cystic changes in prostate acini of Stat5a-deficient mice were not associated with increased prostate size or morphologic hallmarks of epithelial hyperplasia. Instead, immunohistochemistry of the prostate-specific secretory marker, probasin, suggested that hypersecretory function of the epithelium could underlie local congestion and cyst formation in prostates of Stat5a-null mice. Serum testosterone and PRL levels were normal in Stat5a knockout mice, but prostate PRL receptor expression was reduced as determined by immunohistochemistry. Expression levels or activation states of other PRL signal transduction proteins, including Stat5b, Stat3, Stat1, ERK1, and ERK2 were not altered. The present study offers the first evidence for a direct role of Stat5a in the maintenance of normal tissue architecture and function of the mouse prostate.
Author List
Nevalainen MT, Ahonen TJ, Yamashita H, Chandrashekar V, Bartke A, Grimley PM, Robinson GW, Hennighausen L, Rui HMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Cell Division
DNA-Binding Proteins
Epithelial Cells
Epithelium
Male
Mice
Mice, Knockout
Milk Proteins
Prolactin
Prostate
Prostatic Diseases
Receptors, Prolactin
Reference Values
STAT5 Transcription Factor
Signal Transduction
Testosterone
Trans-Activators
