Browsing by Subject "HTRA1"

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    HtrA1 loss is related to aggressive behavior parameters in sentinel node positive breast cancer
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Franco, Renato; Collina, Francesca; Di Bonito, Maurizio; Botti, Gerardo; Montanaro, Donatella; Di Maio, Luigi; Vincenz, Bruno; Landi, Gabriella; D’Aiuto, Massimiliano; Caraglia, Michele; Baldi, Alfonso
    Aim: HtrA1, a member of the High Temperature Requirement Factor A family of oxidative stress-response proteases seems to play a role as a tumor suppressor, being down-regulated in a series of human cancers during their progression. Particularly, low HtrA1 mRNA levels have been observed in breast cancer patients with more aggressive clinical features. These have been shown to relate to a longer disease free and overall survival, with more pronounced effects in axillary nodes positive patients. Subjects and Methods: We have analyzed for immunohistochemical HtrA1 expression a series of 66 sentinel node positive breast cancers through Tissue Micro Array technology. Results: HtrA1 was absent to low in 29 cases, medium in 19 cases and high in 18 cases. Our data revealed a positive significant relation between HtrA1 expression level and estrogen (p=0,002) and progestinic receptor expression (p=0.003) and a negative correlation with histological grading (p=0.028), proliferation index (p=0.05), common BC histotypes (p=0.040), luminal A and B subtypes (p=0.001), metastasis development (p<0.0001) and local relapse (p<0.0001). Finally, no correlation was recorded between HtrA1 expression level and breast cancer histology type and metastasis to non sentinel nodes. Interestingly HtrA1 loss in SLN metastasis was able to predict positive non sentinel nodes (p=0.001). Conclusions: Low HtrA1 expression is significantly related to breast cancer poor prognosis parameters, and HtrA1 loss in sentinel nodes is related to metastasis of non sentinel nodes, offering a further marker useful for BC prognostic stratification.
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    Induction of high temperature requirement A1, a serine protease, by TGF-beta1 in articular chondrocytes of mouse models of OA
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Xu, Lin; Golshirazian, Imanoel; Asbury, Brian J.; Li, Yefu
    The goal of this study is to determine whether transforming growth factor beta 1 (Tgf-ß1) induces the high temperature requirement A1 (HtrA1) in articular chondrocytes of two mouse models of osteoarthritis (OA). Early onset articular cartilage degeneration in the mouse models was characterized by histology. Expression profiles of Tgf-ß1, p-Smad1, pSmad2/3 and HtrA1 in knee joints of the mouse models were examined by immunofluorescene. By in vitro and ex vivo experiments, human primary chondrocytes and articular cartilages from femoral condyles of mice were treated with recombinant human TGF-ß1 and an ALK5 chemical inhibitor, SB431542. The level of HTRA1 mRNA in human and mouse articular chondrocytes was examined by real-time PCR. Chondrocyte clusters were present in the articular cartilage of knee joints in the mouse models. Increased expressions of Tgf-ß1, pSmad2/3 and HtrA1 were detected in the articular chondrocyte of knee joints in the mouse models. The increased expressions of p-Smad2/3 and HtrA1 were colocalized in the articular chondrocyte of the knee joints. The expression of p-Smad1 was hardly detectable in the mouse models and their corresponding wild-type littermates. The level of HTRA1 mRNA was increased in human and mouse articular chondrocytes treated with TGF-ß1, compared with that in chondrocytes without the treatment of TGF-ß1. The TGF-ß1-induced expression of HTRA1 in human and mouse articular chondrocytes was inhibited by SB431542. These results suggest that the Tgf-ß1 canonical signaling was activated to induce HtrA1 in the articular chondrocytes of the mouse models of OA.