Disease relevance of ADAM1

• This is the first report of ADAM expression in prostate cancer cell lines [1].
• To determine the relationship between metastasis and ADAM proteins, we compared the mRNA levels of ADAM9, -10, -12, -15, and -17 in sublines of an EBC-1 lung cancer cell line that were highly metastatic to either brain or bone [2].
• We have investigated ADAM expression in human liver cancers and their regulation by several cytokines involved in liver injury [3].
• We aimed to investigate the clinical significance of EGFR ligands and ADAM family in the lysophosphatidic acid-induced pathogenesis of ovarian cancer [4].
• This is the first report to describe expression of any ADAM in a large number of human carcinomas [5].

Psychiatry related information on ADAM1

• Furthermore, given the importance of integrins in maintaining short-term memory, alterations in ADAM proteins or their proteolytic activity could also play a proximal role in the clinico-pathological manifestations of Alzheimer disease [6].
• Is Adam worth more than Eve? The financial impact of gender bias in the federal reimbursement of gynecological procedures [7].
• Dr. William Cullen and Mr. Adam Smith: a case of hypochondriasis [8]?
• The story of Adam and Eve, which depicts a growing self-determination being stymied and coming to grief, is a mythic epitome of this psychodynamic [9].
• The Adam and Eve story as exemplar of an early-life variant of the oedipus complex [10].

High impact information on ADAM1

• Y chromosomes point to Native American Adam [11].
• Recent evidence implicates three ADAMs, fertilin-alpha, fertilin-beta, and meltrin-alpha, in sperm-egg fusion and myoblast fusion [12].
• An interpretation of Michelangelo's Creation of Adam based on neuroanatomy [13].
• The recent studies have also begun to elucidate the substrate specificity and the mechanisms that control ADAM-mediated shedding events that regulate, for example, growth-factor and Notch signalling, and the processing of the amyloid precursor protein [14].
• ADAM sheddases activate, for example, growth factors and cytokines, thus regulating signalling pathways that are important in development and pathological processes such as cancer [14].

Chemical compound and disease context of ADAM1

• Three forms of recombinant ADAM 12 were used in these experiments: the cys-teine-rich domain made in Escherichia coli (rADAM 12-cys), the disintegrin-like and cysteine-rich domain made in insect cells (rADAM 12-DC), and full-length human ADAM 12-S tagged with green fluorescent protein made in mammalian cells (rADAM 12-GFP) [15].
• These data demonstrate for the first time that among the 13 different ADAM species, ADAM12m is highly expressed in human glioblastomas, and suggest the possibility that ADAM12m plays a role in the prominent proliferation of the glioblastomas through shedding of heparin-binding epidermal growth factor [16].
• Moreover, female transgenics expressing ADAM 12-S exhibited increases in body weight, total body fat mass, abdominal fat mass, and herniation, but were normoglycemic and did not exhibit increased serum insulin, cholesterol, or triglycerides [17].
• However, total oculocutaneous albinism (OCA) associated with deafness has been described only once, by Ziprkowski and Adam (Arch Dermatol 89:151-155, 1964) in an inbred family [18].
• The existence of the so-called 'andropause' is an irrefutable fact, although the terms 'SLOH' (symptomatic late-onset hypogonadism) or 'symptomatic ADAM' (androgen deficiency of the aging male) are more accurate [19].

Biological context of ADAM1

• Therefore, the ADAM1/ADAM2 heterodimer is visualized far in advance of the meiotic and spermiogenic phase of spermatogenesis [20].
• The results demonstrate that chondrocyte metalloproteinase expression can vary dependent on cell environment in situ and in vitro, and information on chondrocyte MMP and ADAM gene expression following cytokine (IL-1) or retinoid stimulation [21].
• These assays, which are not yet available, are required to enable subsequent investigation, both in vitro and in vivo, of the specific roles of each ADAM in prostate cancer cell proliferation, cell motility and invasion [1].
• Here we describe experiments which indicate that the only fertilin alpha-like gene in humans is an expressed, but nonfunctional, pseudogene, possibly derived by genetic recombination between the two fertilin alpha genes found in some primates [22].
• BACKGROUND: The metalloprotease-disintegrin family, or ADAM, proteins, are implicated in cell-cell interactions, cell fusion, and cell signaling, and are widely distributed among metazoan phyla [23].

Anatomical context of ADAM1

• In this study, which ADAM was specifically expressed in monocytes stimulated with anti-CD98 antibody or RANKL and which factor(s) was functioning in monocytes as a fusion protein were investigated [24].
• In contrast, the expression of the ADAM1/ADAM2 pair (fertilin alpha/fertilin beta, respectively) is not detected in fetal testis [20].
• Studies using complementary DNA arrays indicated that the ADAM (A disintegrin and metalloproteinase) genes in gastric epithelial cells are differentially expressed after bacterial-epithelial interactions [25].
• In this study, we identified the expression and the regulation of ADAM members (a disintegrin and metalloprotease) at both gene and protein levels during human osteoclast differentiation and activity [26].
• Our results describe the expression and regulation of various ADAMs in human bone cells and the selective expression of ADAM 12L in osteoblasts [26].

Associations of ADAM1 with chemical compounds

• Tumor necrosis factor-alpha converting enzyme (TACE or ADAM17) is a member of the ADAM (a disintegrin and metalloproteinase) family of type I membrane proteins and mediates the ectodomain shedding of various membrane-anchored signaling and adhesion proteins [27].
• A disintegrin and metalloprotease (ADAM) transmembrane proteins have metalloprotease, integrin-binding, intracellular signaling and cell adhesion activities [28].
• Oxidative and osmotic stress signaling in tumor cells is mediated by ADAM proteases and heparin-binding epidermal growth factor [29].
• Lysophosphatidic acid can generate epidermal growth factor receptor (EGFR) signal transactivation involving processing of EGFR ligands by ADAM (a disintegrin and metalloprotease) family metalloproteases [4].
• Metargidin (ADAM-15) is a type I transmembrane glycoprotein belonging to the ADAM (A Disintegrin and Metalloprotease Domain) family of proteins and is widely expressed in different tissues and cell types [30].

Physical interactions of ADAM1

• TACE/ADAM17 is a member of the adamalysin class of zinc-binding metalloproteases or ADAM (a disintegrin and metalloprotease) [31].
• Further studies of the features of TIMP-3 that determine specific binding to both ADAM and glycosaminoglycan are required in order to understand these unique properties [32].

Regulatory relationships of ADAM1

• TIMP-1 inhibition of TRAIL-induced apoptosis does not depend on its ability to inhibit matrix metalloproteinases or ADAM activities and is unrelated to its ability to stabilize active or decoy death receptors [33].
• We have found using RNA interference analysis that a disintegrin and metalloproteinase (ADAM) 10 is responsible for the regulated shedding of the ectodomain of CD46 in apoptotic cells [34].

Other interactions of ADAM1

• Indeed we found that alpha(9)beta(1) bound avidly to the disintegrin domains of ADAM1, 2, 3, and 9 but not to the disintegrin domains of ADAM10 and 17 [35].
• Human ADAM15 is the only ADAM with the RGD motif in the disintegrin domain [35].
• Interestingly, fertilin-alpha, ADAM9, and ADAM11 have potential fusion peptides [24].
• Although this EGFR transactivation reportedly requires a disintegrin and metalloproteinase (ADAM) that sheds the ectodomain of EGFR ligands, the detailed mechanisms are still unknown [36].
• By using inhibitors with differing potency toward different members of the ADAM (a disintegrin and metalloproteinase) family of proteases, we identified ADAM17 as a candidate mediator of stimulated ACE2 shedding [37].

Analytical, diagnostic and therapeutic context of ADAM1

• EXPERIMENTAL DESIGN: We examined the expression of EGFR ligands and ADAM family members in 108 patients with normal ovaries or ovarian cancer, using real-time PCR, immunohistochemistry, and in situ hybridization, and analyzed the clinical roles of these molecules [4].
• RT-PCR using ADAM-specific primers enabled us to identify the expression of ADAM 8, 9, 10, 15, 17, and 28 in both osteoclasts and osteoblasts [26].
• Like ADAM proteins, integrin beta1, alpha3, and alpha6 subunits, and CD9 and CD81 transcripts are expressed in the fetal testis and throughout testicular maturation, as well as, in Sertoli-spermatogenic cell co- cultures [38].
• The recent molecular cloning of the TNF-a converting enzyme (TACE) revealed that this shedding enzyme belongs to a family of metalloproteinases which contain a disintegrin domain (ADAM family) [39].
• ADAM expression was localized by immunohistochemistry [40].

References