Autophagy is a conserved catabolic process that controls organelle quality, removes misfolded or abnormally aggregated proteins and is part of the defense mechanisms against intracellular pathogens. Autophagy contributes to the suppression of tumor initiation by promoting genome stability, cellular integrity, redox balance and proteostasis. On the other hand, once a tumor is established, autophagy can support cancer cell survival and promote epithelial‑to‑mesenchymal transition.
View Article and Find Full Text PDFGermline inactivating mutations in the BRCA1 gene lead to an increased lifetime risk of ovarian and breast cancer (BC). Most BRCA1-associated BC are triple-negative tumors (TNBC), aggressive forms of BC characterized by a lack of expression of estrogen and progesterone hormone receptors (HR) and HER2. How BRCA1 inactivation may favor the development of such a specific BC phenotype remains to be elucidated.
View Article and Find Full Text PDFCancers (Basel)
December 2021
Cell-to-cell adhesion is a key element in epithelial tissue integrity and homeostasis during embryogenesis, response to damage, and differentiation. Loss of cell adhesion and gain of mesenchymal features, a phenomenon known as epithelial to mesenchymal transition (EMT), are essential steps in cancer progression. Interestingly, downregulation or degradation by endocytosis of epithelial adhesion molecules (e.
View Article and Find Full Text PDFThe arterial form of thoracic outlet syndrome is rare and is associated with anatomic anomalies, generally a cervical rib. It has a varied range of manifestations. The aim of this article is to describe two cases with different clinical presentations: microembolization and aneurysm.
View Article and Find Full Text PDFAutophagy is an intracellular catabolic process that is increasingly being recognized as a crucial factor in several human diseases including cancers. Mounting evidence suggests that autophagy allows tumor cells to overcome otherwise fatal stresses and to increase dissemination. Nevertheless, how autophagy controls these processes and in particular how it impinges on cell-cell adhesion is still poorly understood.
View Article and Find Full Text PDFSince publication of the article, the authors were notified by ATCC that the cell line HCC1395 (ATCC® CRL-2324™ Lot 62235652) suffered a "low level of cell line cross-contamination" with another cell line.
View Article and Find Full Text PDFInactivation of p53 contributes significantly to the dismal prognosis of breast tumors, most notably triple-negative breast cancers (TNBCs). How the relief from p53 tumor suppressive functions results in tumor cell aggressive behavior is only partially elucidated. In an attempt to shed light on the implication of microRNAs in this context, we discovered a new signaling axis involving p53, miR-30a and ZEB2.
View Article and Find Full Text PDFLoss of expression of miR-200 family members has been implicated in cellular plasticity, a phenomenon that accounts for epithelial-to-mesenchymal transition (EMT) and stem-like features of many carcinomas and is considered a major cause of tumor aggressiveness and drug resistance. Nevertheless, the mechanisms of miR-200 downregulation in breast cancer are still largely unknown. Here we show that miR-200c expression inversely correlates with miR-200c/miR-141 locus methylation in triple-negative breast tumors (TNBC).
View Article and Find Full Text PDFBackground: DNA methylation is an important epigenetic mechanism of transcriptional control that plays an essential role in several cellular functions. Aberrant DNA methylation in cancer has been frequently associated with downregulation of microRNAs and protein coding genes, such as miR-200c/miR-141 cluster and E-cadherin. Current strategies to assess DNA methylation, including bisulfite treatment-based assays, tend to be time-consuming and may be quite expensive when a precise appraisal is required.
View Article and Find Full Text PDFIncreasing evidence indicates that invasive properties of breast cancers rely on gain of mesenchymal and stem features, which has suggested that the dual targeting of these phenotypes may represent an appealing therapeutic strategy. It is known that the fraction of stem cells can be enriched by culturing breast cancer cells as mammospheres (MS), but whether these pro-stem conditions favor also the expansion of cells provided of mesenchymal features is still undefined. In the attempt to shed light on this issue, we compared the phenotypes of a panel of 10 breast cancer cell lines representative of distinct subtypes (luminal, HER2-positive, basal-like and claudin-low), grown in adherent conditions and as mammospheres.
View Article and Find Full Text PDFMutations in the BRCA1 tumor suppressor predispose to the development of breast and ovarian cancers. Noticeably, the majority of BRCA1-associated breast cancers are triple-negative (ER-, PR- and HER2-) and display a basal-like phenotype, which are features relatively uncommon among sporadic breast cancers. It is well documented that BRCA1 is involved in a number of cellular functions converging to the maintenance of genomic stability.
View Article and Find Full Text PDFInactivation of the breast cancer susceptibility gene 1 (BRCA1) plays a significant role in the development of a subset of familial breast and ovarian cancers, but increasing evidence points to a role also in sporadic tumors. BRCA1 is a multifunctional nuclear protein involved in the regulation of many nuclear cellular processes, including DNA repair, cell cycle, transcription and chromatin remodeling. To identify novel proteins participating in the BRCA1 network, two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry were used to compare the nuclear-enriched proteome map of BRCA1-deficient and BRCA1-proficient cell lines.
View Article and Find Full Text PDFAims And Background: Colorectal carcinoma patients from hereditary non-polyposis colorectal cancer families are suggested to have a better prognosis than sporadic colorectal carcinoma cases. Since the majority of hereditary non-polyposis colorectal cancer-related colorectal carcinomas are characterized by microsatellite instability due to germline mutations in DNA mismatch repair genes, this is consistent with the prolonged survival observed in sporadic microsatellite instability-positive colorectal carcinoma compared to microsatellite stable cases. However, a fraction of colorectal carcinoma cases belongs to families that, despite fulfilling the clinical criteria for hereditary non-polyposis colorectal cancer, do not carry mismatch repair gene mutations.
View Article and Find Full Text PDFBRCA1-associated tumors are characterized by an elevated genomic instability and peculiar expression profiles. Nevertheless, tailored treatments for BRCA1 mutation carriers have only been partially investigated up to now. The implementation of therapeutic strategies specific for these patients has been in part hindered by the paucity of proper preneoplastic and neoplastic BRCA1-deficient tumor cell models.
View Article and Find Full Text PDFRationale: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. The prevalence of COPD is rising among women and is approaching that of men, but it is not known if sex affects survival.
Objectives: To measure the survival differences between men and women with oxygen-dependent COPD.
Background: Breast cancer in men is an infrequent occurrence, accounting for approximately 1% of all breast tumors with an incidence of about 1:100,000. The relative rarity of male breast cancer (MBC) limits our understanding of the epidemiologic, genetic and clinical features of this tumor.
Methods: From 1997 to 2003, 10 MBC patients were referred to our Institute for genetic counselling and BRCA1/2 testing.
Aim of this study was verifying whether mucin producing colon cancers (CRCs) could develop through a molecular pathway involving microsatellite instability (MSI) and MUC gene alterations. Out of 49 CRCs expressing variable amounts of mucin, 22 (44.9%) were MSI-H and 5 (10.
View Article and Find Full Text PDFBRCA1 and BRCA2 are important for DNA double-strand break repair by homologous recombination, and mutations in these genes predispose to breast and other cancers. Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in base excision repair, a key pathway in the repair of DNA single-strand breaks. We show here that BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis.
View Article and Find Full Text PDFAccurate estimates of breast and ovarian cancer penetrance in BRCA1/2 mutation carriers are crucial in genetic counseling. Estimation is difficult because of the low frequency of mutated alleles and the often-uncertain mechanisms of family ascertainment. We estimated the penetrances of breast and ovarian cancers in carriers of BRCA1/2 mutations by maximizing the retrospective likelihood of the genetic model, given the observed test results, in 568 Italian families screened for germline mutations.
View Article and Find Full Text PDFBiochim Biophys Acta
June 2004
Classical tumour suppressor genes are thought to require mutation or loss of both alleles to facilitate tumour progression. However, it has become clear over the last few years that for some genes, haploinsufficiency, which is loss of only one allele, may contribute to carcinogenesis. These effects can either be directly attributable to the reduction in gene dosage or may act in concert with other oncogenic or haploinsufficient events.
View Article and Find Full Text PDFMutations in BRCA1 and BRCA2 show different expressivity with respect to cancer risk, and allelic heterogeneity may be present in both genes. We collected 179 pedigrees with identified germline mutation (104 BRCA1 and 75 BRCA2), ascertained in six collaborating centers of the Italian Consortium for Hereditary Breast and Ovarian Cancer. Significant heterogeneity was detected for several variables, and a logistic regression model including age of diagnosis in the proband, presence of ovarian cancer in the family, presence of prostate or pancreatic cancer in the family, and presence of male breast cancer in the family proved to be effective in predicting the presence of a mutation in a gene rather than the other.
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