Over-Expression of Activin-βC Is Associated with Murine and Human Prostate Disease

Autor: Karen L Reader, Francesco E. Marino, Gail P. Risbridger, Helen D. Nicholson, Kailun Lee, Edward Ottley, Elspeth Gold
Rok vydání: 2017
Předmět:
Zdroj: Hormones and Cancer. 8:100-107
ISSN: 1868-8500
1868-8497
DOI: 10.1007/s12672-017-0283-8
Popis: Activins are members of the TGF-β superfamily and have been linked to prostate cancer. There are four mammalian activin subunits (βA, βB, βC, and βE) that dimerize to form functional proteins. The role of activin-A (βA-βA) has been relatively well characterized and has been shown to generally inhibit growth in the prostate. In contrast, little is known about the biological function of the βC and βE subunits. Previous work indicated activin-C (βC-βC) to be an antagonist of activin-A. This is important because resistance to activin-A growth inhibition occurs during prostate cancer progression. This paradox is not currently well understood. Hence, we hypothesize that local expression of the activin-βC subunit antagonizes activin-A-dependent growth inhibition and represents a key factor contributing to acquired insensitivity to activin-A observed in prostate cancer progression. To test our hypothesis, we characterized the ventral prostate lobes of 9-month-old transgenic mice over-expressing activin-βC and examined the expression of activin-βA, activin-βC, and the activin intracellular signaling factor, Smad-2, in human prostate diseases. Prostate epithelial cell hyperplasia, low-grade prostatic intraepithelial neoplasia (PIN) lesions, alterations in cell proliferation, and reduced Smad-2 nuclear localization were evident in mice over-expressing activin-βC. Increased activin-βA and -βC subunit immunoreactive scores and decreased Smad-2 nuclear localization were also evident in human prostate cancer. This study suggests that over-expression of activin-βC is associated with murine and human prostate pathologies. We conclude that the activin-βC subunit may have therapeutic and/or diagnostic implications in human prostate disease.
Databáze: OpenAIRE
Externí odkaz: