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Expression of spermidine/spermine N 1 ‐acetyl transferase (SSAT) in human prostate tissues is related to prostate cancer progression and metastasis
Author(s) -
Huang Wei,
Eickhoff Jens C.,
MehraeinGhomi Farideh,
Church Dawn R.,
Wilding George,
Basu Hirak S.
Publication year - 2015
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22996
Subject(s) - prostate cancer , spermine , spermidine , prostate , metastasis , cancer research , prostatectomy , cancer , biochemical recurrence , polyamine , medicine , tissue microarray , pathology , immunohistochemistry , biology , enzyme , biochemistry
Prostate cancer (PCa) in many patients remains indolent for the rest of their lives, but in some patients, it progresses to lethal metastatic disease. Gleason score is the current clinical method for PCa prognosis. It cannot reliably identify aggressive PCa, when GS is ≤ 7. It is shown that oxidative stress plays a key role in PCa progression. We have shown that in cultured human PCa cells, an activation of spermidine/spermine N 1 ‐acetyl transferase (SSAT; EC 2.3.1.57) enzyme initiates a polyamine oxidation pathway and generates copious amounts of reactive oxygen species in polyamine‐rich PCa cells. METHOD We used RNA in situ hybridization and immunohistochemistry methods to detect SSAT mRNA and protein expression in two tissue microarrays (TMA) created from patient's prostate tissues. We analyzed 423 patient's prostate tissues in the two TMAs. RESULTS Our data show that there is a significant increase in both SSAT mRNA and the enzyme protein in the PCa cells as compared to their benign counterpart. This increase is even more pronounced in metastatic PCa tissues as compared to the PCa localized in the prostate. In the prostatectomy tissues from early‐stage patients, the SSAT protein level is also high in the tissues obtained from the patients who ultimately progress to advanced metastatic disease. DISCUSSION Based on these results combined with published data from our and other laboratories, we propose an activation of an autocrine feed‐forward loop of PCa cell proliferation in the absence of androgen as a possible mechanism of castrate‐resistant prostate cancer growth. Prostate 75: 1150–1159, 2015 . © 2015 Wiley Periodicals, Inc.