RESUMO
PSA-RP2 is a variant transcript expressed from the PSA gene that is conserved in gorillas, chimpanzees and humans suggesting a particular relevance for this transcript in these primates. We demonstrated by qRT-PCR that PSA-RP2 is upregulated in prostate cancer compared with benign prostatic hyperplasia tissues. The PSA-RP2 protein was not detected in seminal fluid and was cytoplasmically localised but not secreted from LNCaP or transfected PC3 prostate cells, despite secretion from transfected Cos-7 and HEK293 kidney cell lines. PSA-RP2-transfected PC3 cells showed slightly decreased proliferation and increased migration towards PC3-conditioned medium that could suggest a functional role in prostate cancer.
Assuntos
Regulação Neoplásica da Expressão Gênica , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Sequência de Aminoácidos , Linhagem Celular Tumoral , Humanos , Masculino , Dados de Sequência Molecular , Antígeno Prostático Específico/química , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transporte ProteicoRESUMO
Prostate cancer is associated with significant mortality once the tumour has spread outside the gland. Epithelial-mesenchymal transition (EMT) has been proposed to facilitate this dissemination of tumour cells. In this article we summarize the evidence for EMT in prostate cancer, drawing on the expression of EMT-related markers and the functions of factors known to induce EMT in other systems. We also discuss our recent findings that two members of the tissue kallikrein family of serine proteases, prostate-specific antigen (PSA/KLK3) and kallikrein-related peptidase 4 (KLK4), lead to EMT-like changes in PC3 prostate cancer cells.
Assuntos
Epitélio/patologia , Calicreínas/metabolismo , Mesoderma/patologia , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Animais , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Epitélio/metabolismo , Humanos , Calicreínas/genética , Masculino , Mesoderma/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismoRESUMO
The kallikrein-related ( KLK) protease gene family encodes a subgroup of 15 serine proteases that includes prostate-specific antigen (PSA) or KLK3, the well-known biomarker for prostate cancer. PSA is also a major component of seminal fluid. To date, 10 other KLK serine proteases have been documented as present in seminal fluid (KLKs 1, 2, 4, 5, 6, 8, 10, 11, 13, and 14) and, like PSA, have the potential to contribute to male fertility, either directly or indirectly, by means of their proteolytic activity on seminal coagulum proteins. These KLK enzymes arise predominantly from the glandular epithelium of the prostate and are secreted into the lumen of the prostatic ducts that empty into the urethra upon ejaculation. Given their prostatic origin, they are also being considered increasingly as diagnostic/prognostic targets for prostate cancer. This article reviews the literature on seminal fluid PSA and more recent reports on the detection of other KLKs enzymes in this milieu, and their potential roles in male fertility and prostate cancer. We also discuss recent efforts to determine the proteomic profile of seminal fluid to identify new biomarkers for prostate disease.
Assuntos
Fertilidade , Calicreínas/metabolismo , Antígeno Prostático Específico/metabolismo , Próstata/enzimologia , Neoplasias da Próstata/enzimologia , Proteoma/metabolismo , Sêmen/enzimologia , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Calicreínas/genética , Masculino , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Proteoma/genéticaRESUMO
Several members of the kallikrein-related peptidase family of serine proteases have proteolytic activities that may affect cancer progression; however, the in vivo significance of these activities remains uncertain. We have demonstrated that expression of PSA or KLK4, but not KLK2, in PC-3 prostate cancer cells changed the cellular morphology from epithelial to spindle-shaped, markedly reduced E-cadherin expression, increased vimentin expression and increased cellular migration. These changes are indicative of an epithelial to mesenchymal transition (EMT), a process important in embryonic development and cancer progression. The potential novel role of kallikrein-related peptidases in this process is the focus of this brief review.