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alpha(V)beta(6) integrin expression is induced in the POET and Pten(pc-/-) mouse models of prostatic inflammation and prostatic adenocarcinoma

Garlick, David S.
Li, Jing
Sansoucy, Brian
Wang, Tao
Griffith, Leeanne
FitzGerald, Thomas J
Butterfield, Julie
Charbonneau, Bridget
Violette, Shelia M.
Weinreb, Paul H.
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Abstract

Chronic inflammation is proposed to prime the development of prostate cancer. However, the mechanisms of prostate cancer initiation and development are not completely understood. The alpha(v)beta(6) integrin has been shown to play a role in epithelial development, wound healing and some epithelial cancers [1, 2]. Here, we investigate the expression of alpha(v)beta(6) in mouse models of prostatic inflammation and prostate cancer to establish a possible relationship between inflammation of the prostate, alpha(v)beta(6) expression and the progression of prostate cancer. Using immunohistochemical techniques, we show expression of alpha(v)beta(6) in two in vivo mouse models; the Pten(pc)-/- model containing a prostate- specific Pten tumor suppressor deletion that causes cancer, and the prostate ovalbumin-expressing transgenic (POET) inflammation mouse model. We show that the alpha(v)beta(6) integrin is induced in prostate cancer and inflammation in vivo in these two mouse models. alpha(v)beta(6) is expressed in all the mice with cancer in the Pten(pc-/-) model but not in age-matched wild-type mice. In the POET inflammation model, alpha(v)beta(6) is expressed in mice injected with activated T-cells, but in none of the control mice. In the POET model, we also used real time PCR to assess the expression of Transforming Growth Factor Beta 1 (TGFbeta1), a factor in inflammation that is activated by alpha(v)beta(6). In conclusion, through in vivo evidence, we conclude that alpha(v)beta(6) integrin may be a crucial link between prostatic inflammation and prostatic adenocarcinoma.

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Am J Transl Res. 2012;4(2):165-74. Epub 2012 Apr 10.

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