GCDFP-15 (gross cystic disease fluid protein, 15 kDa) is a secretory marker of apocrine differentiation in breast carcinoma. In human breast cancer cell lines, gene expression is regulated by hormones, including androgens and prolactin. The protein is also known under different names in different body fluids such as gp17 in seminal plasma. GCDFP-15/gp17 is a ligand of CD4 and is a potent inhibitor of T-cell apoptosis induced by sequential CD4/T-cell receptor triggering. We now report that GCDFP-15/gp17 is a protease exhibiting structural properties relating it to the aspartyl proteinase superfamily. Unexpectedly, GCDFP-15/gp17 appears to be related to the retroviral members rather than to the known cellular members of this class. Site-specific mutagenesis of Asp 22 (predicted to be catalytically important for the active site) and pepstatin A inhibition confirmed that the protein is an aspartic-type protease. We also show that, among the substrates tested, GCDFP-15/ gp17 is specific for fibronectin. The study of GCDFP-15/ gp17-mediated proteolysis may provide a handle to understand phenomena as diverse as mammary tumor progression and fertilization.GCDFP-15 (gross cystic disease fluid protein, 15 kDa), also known as prolactin-inducible protein (1), gp17 (2), secretory actin-binding protein (3), and extraparotid glycoprotein (4), is a protein secreted by various exocrine glands, including the seminal vesicle, salivary gland, and sweat glands. This protein is, in addition, expressed by cancer cells derived from a limited number of tissues, among which are prominent primary and secondary breast carcinomas exhibiting an apocrine differentiation (5). The factor exists as a dimer and a tetramer of a glycosylated 17-kDa subunit in various body fluids (6, 7). GCDFP-15 is a highly specific marker for differential cytological diagnosis of metastatic mammary tumors (8), and its expression is up-regulated by androgens, glucocorticoids, and progesterone (9). However, its role in tumors and the prognostic value of its expression are not yet clearly established (10). Studies from our laboratory on the gp17 protein purified from human seminal plasma have shown that it is a ligand for CD4 (11), in turn a T-cell co-receptor playing a key role in antigen recognition and T-cell activation. Further analysis has indicated that early exposure of peripheral blood T-cells to GCDFP-15/gp17 results in the inhibition of CD4 ϩ T-cell apoptosis due to CD4 cross-linking and subsequent T-cell receptor triggering (12). GCDFP-15/gp17 was also found in the post-acrosomal region of ejaculated spermatozoa and remains bound to the sperm cell surface after capacitation, thus implying a possible role in fertilization (13).In this work, we further defined the properties of GCDFP-15/gp17 with the aim of gaining a deeper understanding of its role in tumor progression and reproduction. We found, in fact, that the factor is a retrovirus-like aspartyl protease and has the potential to modify the extracellular matrix by fibronectin degradation. The finding th...
Melanoma is the less common but the most malignant skin cancer. Since the survival rate of melanoma metastasis is about 10–15%, many different studies have been carried out in order to find a more effective treatment. Although the development of target-based therapies and immunotherapeutic strategies has improved chances for patient survival, melanoma treatment still remains a big challenge for oncologists. Here, we collect recent data about the emerging role of melanoma-associated microRNAs (miRNAs) currently available treatments, and their involvement in drug resistance. We also reviewed miRNAs as prognostic factors, because of their chemical stability and resistance to RNase activity, in melanoma progression. Moreover, despite miRNAs being considered small conserved regulators with the limitation of target specificity, we outline the dual role of melanoma-associated miRNAs, as oncogenic and/or tumor suppressive factors, compared to other tumors.
Cancer is the main cause of mortality and morbidity worldwide. Although a large variety of therapeutic approaches have been developed and translated into clinical protocols, the toxic side effects of cancer treatments negatively impact patients, allowing cancer to grow. Brassica metabolites are emerging as new weapons for anti-cancer therapeutics. The beneficial role of the consumption of brassica vegetables, the most-used vegetables in the Mediterranean diet, particularly broccoli, in the prevention of chronic diseases, including cardiovascular diseases, diabetes, and obesity, has been well-documented. In this review, we discuss the anti-tumor effects of the bioactive compounds from Brassica vegetables with regard to the compounds and types of cancer against which they show activity, providing current knowledge on the anti-cancer effects of Brassica metabolites against major types of tumors. In addition, we discuss the impacts of industrial and domestic processing on the compounds’ functional properties before their consumption as well as the main strategies used to increase the content of health-promoting metabolites in Brassica plants through biofortification. Finally, the impacts of microbiota on the compounds’ bioactivity are considered. This information will be helpful for the further development of efficacious anti-cancer drugs.
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