Search results for "hormone-related protein"
showing 10 items of 20 documents
Parathyroid hormone-related protein (PTHrP)-dependent modulation of gene expression signatures in cancer cells
2022
PTHrP is encoded by PTHLH gene which can generate by alternative promoter usage and splicing mechanisms at least three mature peptides of 139, 141 and 173 amino acids with distinct carboxy terminus. PTHrP may undergo proteolytic processing into smaller bioactive forms, comprising an amino terminus peptide, which is the mediator of the "classical" PTH-like effect, as well as midregion and carboxy terminus peptides that act as multifaceted critical regulator of proliferation, differentiation and apoptosis via the reprogramming of gene expression in normal and neoplastic cells. Moreover, a nuclear/nucleolar localization signal sequence is present in the [87-107] domain allowing PTHrP nuclear i…
Current perspectives on parathyroid hormone (PTH) and PTH-related protein (PTHrP) as bone anabolic therapies.
2013
Osteoporosis is characterized by low bone mineral density and/or poor bone microarchitecture leading to an increased risk of fractures. The skeletal alterations in osteoporosis are a consequence of a relative deficit of bone formation compared to bone resorption. Osteoporosis therapies have mostly relied on antiresorptive drugs. An alternative therapeutic approach for osteoporosis is currently available, based on the intermittent administration of parathyroid hormone (PTH). Bone anabolism caused by PTH therapy is mainly accounted for by the ability of PTH to increase osteoblastogenesis and osteoblast survival. PTH and PTH-related protein (PTHrP)-an abundant local factor in bone- interact wi…
Midregion parathyroid hormone-related protein inhibits growth and invasion in vitro and tumorigenesis in vivo of human breast cancer cells.
2001
Parathyroid hormone-related protein (PTHrP) is critical for normal mammary development and is overexpressed by breast cancers. PTHrP is a peptide hormone that undergoes extensive post-translational processing, and PTHrP(38–94)-amide is one of the mature secretory forms of the peptide. In this study, we explored the effect of PTHrP(38–94)-amide in a panel of six breast cancer cell lines “in vitro” and in MDA-MB231 cells “in vivo” specifically examining cell viability, proliferation, invasiveness, and growth in nude mice. PTHrP(38–94)-amide markedly inhibited proliferation and also caused striking toxicity and accelerated cell death in breast cancer cells. In addition, direct injection of PTH…
Regulation of PTHrP and PTH/PTHrP receptor by extracellular Ca2+ concentration and hormones in the breast cancer cell line 8701-BC.
2000
AbstractIt was previously reported that 8701-BC breast tumour cells express the gene for parathyroid hormonerelated peptide (PTHrP) and PTH/PTHrP receptor (PTHrPR) and release immunoreactive PTHrP (iPTHrP) into the extracellular medium. Since the regulation of PTHrP and PTHrPR by breast cancer cells has been poorly investigated so far, we have chosen the 8701- BC cell line as a model system to investigate whether alterations in the extracellular Ca[2+] concentration ([Ca[2+]]) and treatment with some wellknown differentiation agents for breast cells, such as dimethyl sulfoxide, hydrocortisone, progesterone, prolactin, alltrans retinoic acid and transforming growth factorβ1 might (i) modulat…
Anti-senescence and Anti-inflammatory Effects of the C-terminal Moiety of PTHrP Peptides in OA Osteoblasts.
2016
Osteoarthritis (OA) is characterized by degenerative changes in the whole joint leading to physical disability in the elderly population. This condition is associated with altered bone metabolism in subchondral areas suggesting that therapeutic strategies aimed at modifying bone cell metabolism may be of interest. We have investigated the effects of several parathyroid hormone-related protein (PTHrP)-derived peptides (1-37): (N-terminal), (107-111) and (107-139) (C-terminal) on senescence features induced by inflammatory stress in human OA osteoblasts. Incubation of these primary cells with interleukin(IL)-1β led to an increased expression of senescence markers senescence-associated-β-galac…
Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers
2021
BackgroundHypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare.Case SeriesThe present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA)…
Clonal heterogeneity of the growth and invasive response of a human breast carcinoma cell line to parathyroid hormone-related peptide fragments
1997
It has been previously reported that 8701-BC cells, derived from a primary carcinoma of the breast, constitutively express parathyroid hormone (PTH)-related peptide (PTHrP) and PTH/PTHrP receptor (PTH/PTHrP-R) genes, that N-terminal, mid-regional and C-terminal immunoreactive PTHrP can be found in cell conditioned medium and, furthermore, that exogenously added PTHrP (1-34), (67-86) and, to a minor extent, (107-139) are anti-mitogenic but promote Matrigel invasion by this cell line. It has also been reported that PTHrP gene expression is selectively switched on in those 8701-BC clonal lines endowed with a higher proliferation rate and invasive ability in vitro. Here we have first examined t…
Parathyroid hormone-related peptide and 8701-BC breast cancer cell growth and invasion in vitro: evidence for growth-inhibiting and invasion-promotin…
1995
It has been previously reported that 8701-BC cells, derived from a primary carcinoma of the breast, constitutively express parathyroid hormone-related peptide (PTHrP) gene and that N-terminal PTHrP immunoreactivity can be found in cell medium. Here we have firstly measured immunoreactive PTHrP in 8701-BC cell medium using antibodies raised against midregion and C-terminal fragments, and also demonstrated the expression of PTH/PTHrP receptor by 8701-BC cells. Secondly, we have examined the role, if any, elicited by diverse PTHrP domains on 8701-BC cell proliferation, and invasive behaviour in vitro related to production of extracellular proteolytic enzymes. Our data show that PTHrP [1-34], a…
Extracellular matrix regulation of PTHrP and PTH/PTHrP receptor in a human breast cancer cell line
1999
AbstractIt was previously reported that 8701-BC breast cancer cells express the gene for parathyroid hormone-related peptide (PTHrP) and its cognate receptor (PTHrP-R), and release immunoreactive PTHrP in the extracellular medium; it was also found that PTHrP, in turn, exerts a role on the proliferative and invasive behavior in vitro of the same cell line. On the other hand, evidence has been produced that adhesion of 8701-BC cells onto different collagen substrates influences in various ways a number of phenotypic expressions, such as cell growth, motility, invasion of reconstituted basement membrane and production of lytic enzymes of the extracellular matrix (ECM). In light of these previ…
Large-scale genotyping identifies 41 new loci associated with breast cancer risk
2013
Journal article Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ~9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborat…