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Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia.
Cancer Res 2001; 61(4):1686-92CR

Abstract

We identified TMPRSS2 as a gene that is down-regulated in androgen-independent prostate cancer xenograft tissue derived from a bone metastasis. Using specific monoclonal antibodies, we show that the TMPRSS2-encoded serine protease is expressed as a Mr 70,000 full-length form and a cleaved Mr 32,000 protease domain. Mutation of Ser-441 in the catalytic triad shows that the proteolytic cleavage is dependent on catalytic activity, suggesting that it occurs as a result of autocleavage. Mutational analysis reveals the cleavage site to be at Arg-255. A consequence of autocatalytic cleavage is the secretion of the protease domain into the media by TMPRSS2-expressing prostate cancer cells and into the sera of prostate tumor-bearing mice. Immunohistochemical analysis of clinical specimens demonstrates the highest expression of TMPRSS2 at the apical side of prostate and prostate cancer secretory epithelia and within the lumen of the glands. Similar luminal staining was detected in colon cancer samples. Expression was also seen in colon and pancreas, with little to no expression detected in seven additional normal tissues. These data demonstrate that TMPRSS2 is a secreted protease that is highly expressed in prostate and prostate cancer, making it a potential target for cancer therapy and diagnosis.

Authors+Show Affiliations

UroGenesys Inc., Santa Monica, California 90404, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11245484

Citation

Afar, D E., et al. "Catalytic Cleavage of the Androgen-regulated TMPRSS2 Protease Results in Its Secretion By Prostate and Prostate Cancer Epithelia." Cancer Research, vol. 61, no. 4, 2001, pp. 1686-92.
Afar DE, Vivanco I, Hubert RS, et al. Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Cancer Res. 2001;61(4):1686-92.
Afar, D. E., Vivanco, I., Hubert, R. S., Kuo, J., Chen, E., Saffran, D. C., ... Jakobovits, A. (2001). Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Cancer Research, 61(4), pp. 1686-92.
Afar DE, et al. Catalytic Cleavage of the Androgen-regulated TMPRSS2 Protease Results in Its Secretion By Prostate and Prostate Cancer Epithelia. Cancer Res. 2001 Feb 15;61(4):1686-92. PubMed PMID: 11245484.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. AU - Afar,D E, AU - Vivanco,I, AU - Hubert,R S, AU - Kuo,J, AU - Chen,E, AU - Saffran,D C, AU - Raitano,A B, AU - Jakobovits,A, PY - 2001/3/14/pubmed PY - 2001/4/3/medline PY - 2001/3/14/entrez SP - 1686 EP - 92 JF - Cancer research JO - Cancer Res. VL - 61 IS - 4 N2 - We identified TMPRSS2 as a gene that is down-regulated in androgen-independent prostate cancer xenograft tissue derived from a bone metastasis. Using specific monoclonal antibodies, we show that the TMPRSS2-encoded serine protease is expressed as a Mr 70,000 full-length form and a cleaved Mr 32,000 protease domain. Mutation of Ser-441 in the catalytic triad shows that the proteolytic cleavage is dependent on catalytic activity, suggesting that it occurs as a result of autocleavage. Mutational analysis reveals the cleavage site to be at Arg-255. A consequence of autocatalytic cleavage is the secretion of the protease domain into the media by TMPRSS2-expressing prostate cancer cells and into the sera of prostate tumor-bearing mice. Immunohistochemical analysis of clinical specimens demonstrates the highest expression of TMPRSS2 at the apical side of prostate and prostate cancer secretory epithelia and within the lumen of the glands. Similar luminal staining was detected in colon cancer samples. Expression was also seen in colon and pancreas, with little to no expression detected in seven additional normal tissues. These data demonstrate that TMPRSS2 is a secreted protease that is highly expressed in prostate and prostate cancer, making it a potential target for cancer therapy and diagnosis. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11245484/Catalytic_cleavage_of_the_androgen_regulated_TMPRSS2_protease_results_in_its_secretion_by_prostate_and_prostate_cancer_epithelia_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11245484 DB - PRIME DP - Unbound Medicine ER -