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Am J Transl Res 2012;4(2):165-174
Original Article
αVβ6 integrin expression is induced in the poet and PTENpc mouse
models of prostatic inflammation and prostatic adenocarcinoma
David S Garlick*, Jing Li*, Brian Sansoucy, Tao Wang, Leeanne Griffith, TJ FitzGerald, Julie Butterfield, Bridget
Charbonneau, Shelia M Violette, Paul H Weinreb, Timothy L Ratliff, Chun-Peng Liao, Pradip Roy-Burman, Michele
Vietri, Jane B Lian, Gary S Stein, Dario C Altieri, Lucia R Languino
Department of Cancer Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA;
Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA; Purdue
University Center for Cancer Research, Department of Comparative Pathobiology, School of Veterinary Medicine,
Purdue University, West Lafayette, IN; Stromedix, Cambridge, MA; Biogen Idec, Inc., Cambridge, MA; Department
of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA; Prostate Cancer
Discovery and Development Program, Department of Cell Biology and Cancer Center, University of
Massachusetts Medical School, Worcester, MA; Prostate Cancer Discovery and Development Program, The
Wistar Institute Cancer Center, Philadelphia, PA; Prostate Cancer Discovery and Development Program,
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA. *These
Authors contributed equally to this work.
Received March 19, 2012; accepted April 6, 2012; Epub April 10, 2012; Published April 30, 2012
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 αvβ6 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 αvβ6 in mouse models of prostatic inflammation and prostate cancer to establish a
possible relationship between inflammation of the prostate, αvβ6 expression and the progression of prostate
cancer. Using immunohistochemical techniques, we show expression of αvβ6 in two in vivo mouse models; the
PTENpc 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 αvβ6 integrin is
induced in prostate cancer and inflammation in vivo in these two mouse models. αvβ6 is expressed in all the
mice with cancer in the PTENpc model but not in age-matched wild-type mice. In the POET inflammation model,
αvβ6 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 (TGFβ1), a factor in
inflammation that is activated by αvβ6. In conclusion, through in vivo evidence, we conclude that integrin αvβ6 may
be a crucial link between prostatic inflammation and prostatic adenocarcinoma. (AJTR1203002)
Keywords: Prostate cancer, PIN lesion, chronic inflammation, TGFβ1, αVβ6 integrin, AKT.
Address all correspondence to:
Dr. Lucia R Languino
Department of Cancer Biology
Kimmel Cancer Center
Thomas Jefferson University
233 South 10th Street
Philadelphia, PA 19107, USA>
Tel: 215.503.3442; Fax: 215.503.1607
E-mail: Lucia.Languino@ kimmelcancercenter.org
Original Article
αVβ6 integrin expression is induced in the poet and PTENpc mouse
models of prostatic inflammation and prostatic adenocarcinoma
David S Garlick*, Jing Li*, Brian Sansoucy, Tao Wang, Leeanne Griffith, TJ FitzGerald, Julie Butterfield, Bridget
Charbonneau, Shelia M Violette, Paul H Weinreb, Timothy L Ratliff, Chun-Peng Liao, Pradip Roy-Burman, Michele
Vietri, Jane B Lian, Gary S Stein, Dario C Altieri, Lucia R Languino
Department of Cancer Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA;
Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA; Purdue
University Center for Cancer Research, Department of Comparative Pathobiology, School of Veterinary Medicine,
Purdue University, West Lafayette, IN; Stromedix, Cambridge, MA; Biogen Idec, Inc., Cambridge, MA; Department
of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA; Prostate Cancer
Discovery and Development Program, Department of Cell Biology and Cancer Center, University of
Massachusetts Medical School, Worcester, MA; Prostate Cancer Discovery and Development Program, The
Wistar Institute Cancer Center, Philadelphia, PA; Prostate Cancer Discovery and Development Program,
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA. *These
Authors contributed equally to this work.
Received March 19, 2012; accepted April 6, 2012; Epub April 10, 2012; Published April 30, 2012
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 αvβ6 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 αvβ6 in mouse models of prostatic inflammation and prostate cancer to establish a
possible relationship between inflammation of the prostate, αvβ6 expression and the progression of prostate
cancer. Using immunohistochemical techniques, we show expression of αvβ6 in two in vivo mouse models; the
PTENpc 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 αvβ6 integrin is
induced in prostate cancer and inflammation in vivo in these two mouse models. αvβ6 is expressed in all the
mice with cancer in the PTENpc model but not in age-matched wild-type mice. In the POET inflammation model,
αvβ6 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 (TGFβ1), a factor in
inflammation that is activated by αvβ6. In conclusion, through in vivo evidence, we conclude that integrin αvβ6 may
be a crucial link between prostatic inflammation and prostatic adenocarcinoma. (AJTR1203002)
Keywords: Prostate cancer, PIN lesion, chronic inflammation, TGFβ1, αVβ6 integrin, AKT.
Address all correspondence to:
Dr. Lucia R Languino
Department of Cancer Biology
Kimmel Cancer Center
Thomas Jefferson University
233 South 10th Street
Philadelphia, PA 19107, USA>
Tel: 215.503.3442; Fax: 215.503.1607
E-mail: Lucia.Languino@ kimmelcancercenter.org
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