Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2gene.
This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Serine proteases are known to be involved in many physiological and pathological processes. This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. The biological function of this gene is unknown.
TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1, through gene fusion. TMPRSS2-ERG fusion gene is the most frequent, present in 40% - 80% of prostate cancers in humans. ERG overexpression contributes to development of androgen-independence in prostate cancer through disruption of androgen receptor signaling.
^Paoloni-Giacobino A, Chen H, Peitsch MC, Rossier C, Antonarakis SE (Nov 1997). "Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3". Genomics44 (3): 309–20. doi:10.1006/geno.1997.4845. PMID9325052.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Lin B, Ferguson C, White JT, et al. (1999). "Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2". Cancer Res.59 (17): 4180–4. PMID10485450.
Afar DE, Vivanco I, Hubert RS, et al. (2001). "Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia". Cancer Res.61 (4): 1686–92. PMID11245484.
Soller MJ, Isaksson M, Elfving P, et al. (2006). "Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate cancer". Genes Chromosomes Cancer45 (7): 717–9. doi:10.1002/gcc.20329. PMID16575875.
Winnes M, Lissbrant E, Damber JE, Stenman G (2007). "Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer". Oncol. Rep.17 (5): 1033–6. doi:10.3892/or.17.5.1033. PMID17390040.
Tu JJ, Rohan S, Kao J, et al. (2007). "Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues". Mod. Pathol.20 (9): 921–8. doi:10.1038/modpathol.3800903. PMID17632455.