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Increased expression of tumor-associated trypsin inhibitor, TATI, in prostate cancer and in androgen-independent 22Rv1 cells

Paju, Annukka; Hotakainen, Kristina; Cao, Yue LU ; Laurila, Timo; Gadaleanu, Virgil; Hemminki, Akseli; Stenman, Ulf-Hakan and Bjartell, Anders LU (2007) In European Urology 52(6). p.1670-1681
Abstract
Objectives: Tumor-associated-trypsin inhibitor (TATI) is frequently coexpressed with trypsinogen in tumors. Recently, we found expression of trypsinogens in prostate cancer. We have now studied whether TATI is also expressed in prostate cancer and if TATI expression is associated with Gleason grade, proliferation, and neuroendocrine differentiation. Methods: Expression of TATI and prostate-specific antigen (PSA) was studied by immunohistochemistryand in situ hybridization, and that of chromogranin A (CgA) and Ki-67 by immunohistochemistry. Immunofluorometric assays were used to quantify TATI and PSA in serum from prostate cancer patients and in medium of 22Rv1 prostate cancer cells. Results: TATI expression was weak in benign prostatic... (More)
Objectives: Tumor-associated-trypsin inhibitor (TATI) is frequently coexpressed with trypsinogen in tumors. Recently, we found expression of trypsinogens in prostate cancer. We have now studied whether TATI is also expressed in prostate cancer and if TATI expression is associated with Gleason grade, proliferation, and neuroendocrine differentiation. Methods: Expression of TATI and prostate-specific antigen (PSA) was studied by immunohistochemistryand in situ hybridization, and that of chromogranin A (CgA) and Ki-67 by immunohistochemistry. Immunofluorometric assays were used to quantify TATI and PSA in serum from prostate cancer patients and in medium of 22Rv1 prostate cancer cells. Results: TATI expression was weak in benign prostatic epithelium and moderate to strong in prostate cancer and high-grade prostatic intraepithelial neoplasia. There was no correlation between TATI and Ki-67 immunostaining in a tissue microarray of 115 prostate cancer cores, but strong expression of TATI was associated with higher Gleason grade (p = 0.002) and CgA immunostaining intensity (p = 0.012). Serum TATI was elevated in 44% (29 of 66) of patients with prostate cancer, and the levels correlated with serum PSA (p < 0.0001, r = 0.306). DU145, PC-3, LNCaP, and 22Rv1 cells contained TATI mRNA as determined by RT-PCR, but only 22Rv1 cells produced detectable TATI protein. The synthetic androgen R1881 decreased secretion of TATI from 22Rv1 cells. Conclusions: We demonstrate for the first time that TATI is expressed in the benign and malignant prostate. Increased TATI protein expression is found in high-grade tumors and in 22Rv1 cells in which it is regulated by androgens. (c) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
protease inhibitor, 22RV1 cells, Kallikreins, immunohistochemistry, in situ hybridization
in
European Urology
volume
52
issue
6
pages
1670 - 1681
publisher
Elsevier
external identifiers
  • wos:000251409600021
  • scopus:35748961384
ISSN
1873-7560
DOI
10.1016/j.eururo.2007.01.096
language
English
LU publication?
yes
id
a71a8e10-7c84-41df-83f9-0878336d4e31 (old id 966319)
date added to LUP
2008-01-30 07:52:29
date last changed
2017-10-08 04:25:08
@article{a71a8e10-7c84-41df-83f9-0878336d4e31,
  abstract     = {Objectives: Tumor-associated-trypsin inhibitor (TATI) is frequently coexpressed with trypsinogen in tumors. Recently, we found expression of trypsinogens in prostate cancer. We have now studied whether TATI is also expressed in prostate cancer and if TATI expression is associated with Gleason grade, proliferation, and neuroendocrine differentiation. Methods: Expression of TATI and prostate-specific antigen (PSA) was studied by immunohistochemistryand in situ hybridization, and that of chromogranin A (CgA) and Ki-67 by immunohistochemistry. Immunofluorometric assays were used to quantify TATI and PSA in serum from prostate cancer patients and in medium of 22Rv1 prostate cancer cells. Results: TATI expression was weak in benign prostatic epithelium and moderate to strong in prostate cancer and high-grade prostatic intraepithelial neoplasia. There was no correlation between TATI and Ki-67 immunostaining in a tissue microarray of 115 prostate cancer cores, but strong expression of TATI was associated with higher Gleason grade (p = 0.002) and CgA immunostaining intensity (p = 0.012). Serum TATI was elevated in 44% (29 of 66) of patients with prostate cancer, and the levels correlated with serum PSA (p &lt; 0.0001, r = 0.306). DU145, PC-3, LNCaP, and 22Rv1 cells contained TATI mRNA as determined by RT-PCR, but only 22Rv1 cells produced detectable TATI protein. The synthetic androgen R1881 decreased secretion of TATI from 22Rv1 cells. Conclusions: We demonstrate for the first time that TATI is expressed in the benign and malignant prostate. Increased TATI protein expression is found in high-grade tumors and in 22Rv1 cells in which it is regulated by androgens. (c) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.},
  author       = {Paju, Annukka and Hotakainen, Kristina and Cao, Yue and Laurila, Timo and Gadaleanu, Virgil and Hemminki, Akseli and Stenman, Ulf-Hakan and Bjartell, Anders},
  issn         = {1873-7560},
  keyword      = {protease inhibitor,22RV1 cells,Kallikreins,immunohistochemistry,in situ hybridization},
  language     = {eng},
  number       = {6},
  pages        = {1670--1681},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {Increased expression of tumor-associated trypsin inhibitor, TATI, in prostate cancer and in androgen-independent 22Rv1 cells},
  url          = {http://dx.doi.org/10.1016/j.eururo.2007.01.096},
  volume       = {52},
  year         = {2007},
}