Disease relevance of Proliferin

• Reactivation of proliferin gene expression is associated with increased angiogenesis in a cell culture model of fibrosarcoma tumor progression [1].
• Proliferin enhances microvilli formation and cell growth of neuroblastoma cells [2].

High impact information on Proliferin

• Stimulation and inhibition of angiogenesis by placental proliferin and proliferin-related protein [3].
• Proliferin (PLF) gene expression provides a model of growth-related transcriptional activation in mouse cells [4].
• In trophoblasts, the lack of JunB causes a deregulation of proliferin, matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) gene expression, resulting in a defective neovascularization of the decidua [5].
• In contrast, the upstream region from a second proliferin gene is only weakly inducible in transfected cell cultures, even though these two promoter regions share 97% nucleotide sequence homology [6].
• The sequences upstream of a proliferin gene have been isolated, linked to a reporter gene, and transfected into mouse cell cultures [6].

Biological context of Proliferin

• Co-localization of elements required for phorbol ester stimulation and glucocorticoid repression of proliferin gene expression [4].
• Because of its relationship to prolactin and growth hormone and its association with cell proliferation, the protein has been called "proliferin."[7]
• From a cDNA plasmid library prepared from poly(A)+ placental RNA, two types of proliferin-related clones were isolated, differing in intensity of hybridization to proliferin cDNA [8].
• Analysis of the Sph element revealed that mutation of Sph repeats I or III abolished serum responsiveness of the PLF gene promoter, and mutation of Sph repeat III decreased protein binding to this element [9].
• This heterogeneity is probably due to asynchrony in the population and may point to a correlation between the time of proliferin expression and the time of entry of a cell into S phase [10].

Anatomical context of Proliferin

• The mitogen-regulated protein/proliferin transcript is degraded in primary mouse embryo fibroblast but not 3T3 nuclei: altered RNA processing correlates with immortalization [11].
• We conclude that proliferin is a placental hormone that is synthesized in certain mouse cell lines during active growth [8].
• Mitogen-regulated protein/proliferin mRNA is undetectable in northern blots of RNA from (mortal) MEFs, whereas it is readily detected in immortal 3T3 cell lines derived from the MEFs [11].
• The serum-inducible expression of proliferin genes in BALB/c 3T3 cells was found to be dependent on both protein synthesis and an extended presence of serum in the medium [10].
• Placentas lacking GATA-2 secrete significantly less angiogenic activity than wild-type placentas as measured in an endothelial cell migration assay, consistent with a reduction in expression of the angiogenic hormone proliferin [12].

Associations of Proliferin with other chemical compounds

• Proliferin binding to endothelial cells is blocked by the addition of mannose 6-phosphate, as is the ability of both recombinant and placental-derived proliferin to stimulate the migration of capillary endothelial cells in vitro and to induce neovascularization in the rat cornea [13].
• Asbestos-induced gene expression was inhibited by millimolar levels of N-acetylcysteine (NAC), supporting a linkage between: (i) induced oxidant stress that was sufficient to promote morphological transformation; (ii) induction of proliferin expression [14].
• Compounds likely to promote transformation (nickel sulphate, benzyl peroxide and t-butyl hydroperoxide) were also effective and apparently selective, proliferin inducers in C3H/10T1/2 and primary murine fibroblasts [15].
• Proliferin expression measured in near-confluent cultures was induced up to 10-fold during the 36-hr period following di-n-butyltin dichloride exposure and was accompanied by increased accumulation of transcripts from many genes regulated by oxidative stresses, growth-inducing agents, and/or other promoting agents (asbestos, superoxide radicals ) [16].

Gene context of Proliferin

• Proliferin, a prolactin/growth hormone-like peptide represses myogenic-specific transcription by the suppression of an essential serum response factor-like DNA-binding activity [17].
• Large cells that expressed the trophoblast giant cell-specific gene Plf (encoding Proliferin) invaded during the early postimplantation period in a pattern tightly associated with spiral arteries [18].
• All of the other genes in this hormone family, including those encoding mPRL, mouse placental lactogens I and II, and mouse proliferin and proliferin-related protein, map to chromosome 13 [19].
• Negative GREs contribute to the regulation of the hypothalamic-pituitary-adrenal (HPA) axis (POMC and CRH), bone (osteocalcin) and skin (keratins) function, inflammation (IL-1beta), angiogenesis (proliferin) and lactation (prolactin) [20].
• They should also be useful in examining the significance of binding of ligands, such as transforming growth factor-beta 1 precursor and proliferin to this receptor [21].

Analytical, diagnostic and therapeutic context of Proliferin

• Initiation of transcription occurs at the same site in the transfected DNA as in endogenous proliferin genes expressed in placental tissue and in cell cultures [6].
• Proliferin RNA levels were found to be heterogeneous among serum-stimulated cells analyzed by in situ hybridization [10].
• The murine proliferin gene family, which has been shown to respond consistently to tumor promoters and other cellular pro-oxidant agents in C3H/10T1/2 cells, was used to monitor responses after treatment of these cell cultures with toxic, pro-oxidant asbestos fibres [14].
• A family of proliferin genes was discovered on a microarray analysis of hematopoiesis supportive stromal cell lines [22].

References