Increased expression of tumor-associated trypsin inhibitor, TATI, in prostate cancer and in androgen-independent 22Rv1 cells.
OBJECTIVE
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 immunohistochemistry and 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.
Paju
Annukka
A
Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland. annukka.paju@hus.fi
Hotakainen
Kristina
K
Cao
Yue
Y
Laurila
Timo
T
Gadaleanu
Virgil
V
Hemminki
Akseli
A
Stenman
Ulf-Håkan
UH
Bjartell
Anders
A
D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D046888:Tissue Array Analysis; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000032:analysis* / Q000097:blood / Q000235:genetics
D015741:Metribolone; D014359:Trypsin Inhibitor, Kazal Pancreatic