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LNCaP
LNCaP cells are a cell line of human cells commonly used in the field of oncology. LNCaP cells are androgen-sensitive human prostate adenocarcinoma cells derived from the left supraclavicular lymph node metastasis from a 50-year-old caucasian male in 1977. They are adherent epithelial cells growing in aggregates and as single cells. One major obstacle to conducting the most clinically relevant prostate cancer (PCa) research has been the lack of cell lines that closely mimic human disease progression. Two hallmarks of metastatic human prostate cancer include the shift of aggressive PCa from androgen-sensitivity to an Androgen Insensitive (AI) state, and the propensity of PCa to metastasize to bone. Although the generation of AI cell lines has been quite successful as demonstrated in the “classic” cell lines DU145 and PC3, the behavior of these cells in bone does not fully mimic clinical human disease. It is well established that human PCa bone metastasis form osteoblastic l ...
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Androgen Receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the Cell nucleus, nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor. The main function of the androgen receptor is as a DNA-binding protein, DNA-binding transcription factor that Gene expression regulation, regulates gene expression; however, the androgen receptor has other functions as well. Androgen-regulated genes are critical for the development and maintenance of the male sexual phenotype. Function Effect on development In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha reductase, 5-alpha-reductase to dihydrot ...
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Prostate Cancer
Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, typically blood tests that check for prostate-specific antigen (PSA) levels. Those with high levels of PSA in their blood are at increased risk for developing prostate cancer. Diagnosis requires a prostate biopsy, biopsy of the prostate. If cancer is present, the pathologist assigns a Gleason score; a higher score represents a more dangerous tumor. Medical imaging is performed to look for cancer that has spread outside the prostate. Based on the Gleason score, PSA levels, and imaging results, a cancer case is assigned a cancer staging, stage 1 to 4. A higher stage signifies a more advanced, more dangerous disease. Most prostate tumors remain small and cause no health problems. These are managed with active surveillance of prostate cancer, ...
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DU145
DU145 (DU-145) is a human prostate cancer cell line. DU145, PC3, and LNCaP are considered to be the standard prostate cancer cell lines used in therapeutic research. The DU145 cell line was derived from a central nervous system metastasis, of primary prostate adenocarcinoma origin, removed during a parieto-occipital craniotomy of a 69-year-old, white male. DU145 are not hormone-sensitive and do not express prostate-specific antigen (PSA). DU145 cells have moderate metastatic potential compared to PC3 cells, which have high metastatic potential. Research on castration-resistant prostate cancer Castration-resistant prostate cancer (CRPC) is prostate cancer that progresses despite extremely low testosterone in the body often due to medical castration. Unlike many other types of prostate cancer, CRPC do not need normal testosterone levels, but they still require regular androgen receptors (AR). Effects of NEK6 alteration NEK6 inhibition is a potential treatment for CRPC due to ...
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Y Chromosome
The Y chromosome is one of two sex chromosomes in therian mammals and other organisms. Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining chromosome because the presence of the Y chromosome causes offspring produced in sexual reproduction to be of male sex. In mammals, the Y chromosome contains the SRY gene, which triggers development of male gonads. The Y chromosome is passed only from male parents to male offspring. Overview Discovery The Y chromosome was identified as a sex-determining chromosome by Nettie Stevens at Bryn Mawr College in 1905 during a study of the mealworm ''Tenebrio molitor''. Edmund Beecher Wilson independently discovered the same mechanisms the same year, working with Hemiptera. Stevens proposed that chromosomes always existed in pairs and that the smaller chromosome (now labelled "Y") was the pair of the X chromosome discovered in 1890 by Hermann Henking. She realized that th ...
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Osteonectin
Osteonectin (ON) also known as secreted protein acidic and rich in cysteine (SPARC) or basement-membrane protein 40 (BM-40) is a protein that in humans is encoded by the ''SPARC'' gene. Osteonectin is a glycoprotein in the bone that binds calcium. It is secreted by osteoblasts during bone formation, initiating mineralization and promoting mineral crystal formation. Osteonectin also shows affinity for collagen in addition to bone mineral calcium. A correlation between osteonectin over-expression and ampullary cancers and chronic pancreatitis has been found. Gene The human SPARC gene is 26.5 kb long, and contains 10 exons and 9 introns and is located on chromosome 5q31-q33. Structure Osteonectin is a 40 kDa acidic and cysteine-rich glycoprotein consisting of a single polypeptide chain that can be broken into 4 domains: 1) a Ca2+ binding domain near the glutamic acid-rich region at the amino terminus (domain I), 2) a cysteine-rich domain (II), 3) a hydrophilic region ( ...
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RANKL
Receptor activator of nuclear factor kappa- ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the ''TNFSF11'' gene. RANKL is known as a type II membrane protein and is a member of the tumor necrosis factor (TNF) superfamily. RANKL has been identified to affect the immune system and control bone regeneration and remodeling. RANKL is an apoptosis regulator gene, a binding partner of osteoprotegerin (OPG), a ligand for the receptor RANK and controls cell proliferation by modifying protein levels of Id4, Id2 and cyclin D1. RANKL is expressed in several tissues and organs including: skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoblast, mammary gland epithelial cells, prostate and pancreas. Variation in concentration levels of RANKL througho ...
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Osteocalcin
Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a small (49-amino-acid) noncollagenous protein hormone found in bone and dentin, first identified as a calcium-binding protein. Because osteocalcin has gla domains, its synthesis is vitamin K2-dependent. In humans, osteocalcin is encoded by the ''BGLAP'' gene. Its receptors include GPRC6A, GPR158, and possibly a third, yet-to-be-identified receptor. There is evidence that GPR37 might be the third osteocalcin receptor. Function Osteocalcin is secreted solely by osteoblasts and is thought to play a role in the body's metabolic regulation. In its carboxylated form, calcium is bound directly to the bone and thus concentrates here. In its uncarboxylated form, osteocalcin acts as a hormone in the body, signalling in the pancreas, fat, muscle, testes, and brain. * In the pancreas, osteocalcin acts on beta cells, causing beta cells in the pancreas to release more insulin. * In fat cel ...
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Bone Sialoprotein
Bone sialoprotein (BSP) is a component of mineralized tissues such as bone, dentin, cementum and calcified cartilage. BSP is a significant component of the bone extracellular matrix and has been suggested to constitute approximately 8% of all non-collagenous proteins found in bone and cementum. BSP, a SIBLING protein, was originally isolated from bovine cortical bone as a 23-kDa glycopeptide with high sialic acid content. The human variant of BSP is called bone sialoprotein 2 also known as cell-binding sialoprotein or integrin-binding sialoprotein and is encoded by the ''IBSP'' gene. Structure Native BSP has an apparent molecular weight of 60-80 kDa based on SDS-PAGE, which is a considerable deviation from the predicted weight (based on cDNA sequence) of approximately 33 kDa. The mammalian BSP cDNAs encode for proteins averaging 317 amino acids, which includes the 16-residue preprotein secretory signal peptide. Among the mammalian cDNAs currently characterized, there is ...
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Alkaline Phosphatase
The enzyme alkaline phosphatase (ALP, alkaline phenyl phosphatase, also abbreviated PhoA) is a phosphatase with the physiological role of dephosphorylating compounds. The enzyme is found across a multitude of organisms, prokaryotes and eukaryotes alike, with the same general function, but in different structural forms suitable to the environment they function in. Alkaline phosphatase is found in the periplasmic space of '' E. coli'' bacteria. This enzyme is heat stable and has its maximum activity at high pH. In humans, it is found in many forms depending on its origin within the body – it plays an integral role in metabolism within the liver and development within the skeleton. Due to its widespread prevalence in these areas, its concentration in the bloodstream is used by diagnosticians as a biomarker in helping determine diagnoses such as hepatitis or osteomalacia. The level of alkaline phosphatase in the blood is checked through the ALP test, which is often par ...
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Osteoprotegerin
Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF) or tumour necrosis factor receptor superfamily member 11B (TNFRSF11B), is a cytokine receptor of the tumour necrosis factor (TNF) receptor superfamily encoded by the ''TNFRSF11B'' gene. OPG was first discovered as a novel secreted TNFR related protein that played a role in the regulation of bone density and later for its role as a decoy receptor for receptor activator of nuclear factor kappa-B ligand ( RANKL). OPG also binds to TNF-related apoptosis-inducing ligand ( TRAIL) and inhibits TRAIL induced apoptosis of specific cells, including tumour cells. Other OPG ligands include syndecan-1, glycosaminoglycans, von Willebrand factor, and factor VIII-von Willebrand factor complex. OPG has been identified as having a role in tumour growth and metastasis, heart disease, immune system development and signalling, mental health, diabetes, and the prevention of pre-eclampsia and osteoporosis during pre ...
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Hydroxyapatite
Hydroxyapatite (International Mineralogical Association, IMA name: hydroxylapatite) (Hap, HAp, or HA) is a naturally occurring mineral form of calcium apatite with the Chemical formula, formula , often written to denote that the Crystal structure, crystal unit cell comprises two entities. It is the Hydroxy group, hydroxyl endmember of the complex apatite, apatite group. The ion can be replaced by fluorine, fluoride or chlorine, chloride, producing fluorapatite or chlorapatite. It crystallizes in the hexagonal (crystal system), hexagonal crystal system. Pure hydroxyapatite powder is white. Naturally occurring apatites can, however, also have brown, yellow, or green colorations, comparable to the discolorations of dental fluorosis. Up to 50% by volume and 70% by weight of human bone is a modified form of hydroxyapatite, known as bone mineral. Carbonated calcium-deficient hydroxyapatite is the main mineral of which dental enamel and dentin are composed. Hydroxyapatite crystals a ...
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