Disease relevance of Prl2c2

• Proliferin enhances microvilli formation and cell growth of neuroblastoma cells [1].
• However, transient constitutive expression of MyoD by the Moloney sarcoma virus long terminal repeat did not override the effect of PLF [2].
• Transcription from a cloned PLF promoter is inducible by phorbol esters, and this induction involves a region of 31 bp that includes an AP-1 site and a cluster of sites similar to the simian virus 40 (SV40) SphI element [3].
• We now report that PLF gene expression can also occur in a progressive fibrosarcoma mouse tumor cell model [4].
• Cardiac Mrp1 may play a role in protecting the heart from Adriamycin-induced cardiomyopathy by effluxing HNE conjugates [5].

High impact information on Prl2c2

• The mouse placenta secretes an angiogenic activity during the middle of pregnancy that corresponds primarily to PLF, but later in gestation releases a factor that inhibits angiogenesis, which was identified as PRP [6].
• Incubation of placental tissue with PLF led to the specific binding of this hormone to capillary endothelial cells [6].
• Co-localization of elements required for phorbol ester stimulation and glucocorticoid repression of proliferin gene expression [3].
• 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 [7].
• The sequences upstream of a proliferin gene have been isolated, linked to a reporter gene, and transfected into mouse cell cultures [7].

Biological context of Prl2c2

• By nucleotide sequence analysis, a strongly hybridizing clone was found to be nearly identical to the proliferin cDNA clone isolated from a library prepared from mRNA of a growing mouse fibroblastic cell line [8].
• 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].
• PLF1 was detected and found to be differentially regulated during myogenesis in the rodent myogenic cell line C2C12 [2].
• In conclusion, PLF selectively represses myogenic-specific transcription within the actin multigene family by suppressing the level and/or activity of a trans-acting factor (CBF) that modulates multiple muscle-specific genes [2].
• 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 [9].

Anatomical context of Prl2c2

• 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 [10].
• We conclude that proliferin is a placental hormone that is synthesized in certain mouse cell lines during active growth [8].
• These data suggest that cAMP levels can regulate trophoblast giant cell differentiation and, consequently, the amount of PLF and PRP secretion [11].
• Analyses of cells stably transfected with PLF showed reduced levels of MyoD mRNA, a recently identified gene that is sufficient to convert pluripotential 10T1/2 cells into myoblasts [2].
• Moreover, the serum concentration of PLF during pregnancy varied directly with the level of PLF mRNA in the placenta and with the number of placentas per animal [12].

Associations of Prl2c2 with chemical compounds

• Using an antiserum prepared against a synthetic proliferin fusion protein, we show that proliferin is secreted as a glycoprotein by minced placental tissue and that it differs from mouse placental lactogen [8].
• Cyclic adenosine 3',5'-monophosphate stimulation of placental proliferin and proliferin-related protein secretion [11].
• Proliferin secreted by cultured cells binds to mannose 6-phosphate receptors [13].
• To determine if proliferin genes respond to tumor promoters in vivo, RNA was extracted from the whole skin of SENCAR mice after single applications of 2 or 20 microg 12-O-tetradecanoylphorbol-13-acetate (TPA); 3.2 or 32 nmole), 20 or 40 mg benzoyl peroxide (BPO; 83, 165 micromole), or acetone vehicle alone (2.72 mmole) [14].
• The transport of etoposide, E217betaG, vincristine, and doxorubicin into the brain was not affected by the lack of mrp1 [15].

Regulatory relationships of Prl2c2

• The increase in the number of PLF-producing cells was accompanied by an increase in the number of cells expressing both PLF and mouse placental lactogen-I [11].
• On the basis of the results of our studies with cells in culture we propose that the production of MRP in the placenta is regulated similarly to prolactin [16].
• Consistent with its response to other oxidant chemicals, induction of proliferin by ammonium metavanadate was inhibited almost completely by the antioxidant N-acetylcysteine (8 mM) [17].
• Our results, therefore, suggest that overexpression of PKCdelta induces transcriptional repression of proliferin, thereby resulting in inhibition of cell proliferation [18].

Other interactions of Prl2c2

• 5. These cells did not express Plf, but rather expressed the spongiotrophoblast-specific gene Tpbp [10].
• Proliferin is a recently described, prolactin-related protein whose mRNA appears in several murine cell lines during active growth [8].
• Individual cells contained both PLF and placental lactogen II [12].
• Rodents deficient in three known ABC family transporters (MRP1, MRP2, and MDR1a/1b) exhibited urinary arsenic levels similar or greater than those in wild-type rodents; however, administration of MK571, an MRP inhibitor, reduced urinary arsenic excretion by almost 50% [19].
• Participation of multiple factors, including proliferin, in the inhibition of myogenic differentiation [20].

Analytical, diagnostic and therapeutic context of Prl2c2

• By immunohistochemical staining and in situ hybridization PLF protein and messenger RNA (mRNA) were localized to the trophoblastic giant cells [12].
• 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 [7].
• A family of proliferin genes was discovered on a microarray analysis of hematopoiesis supportive stromal cell lines [21].
• METHODS: The transport of radiolabeled etoposide, 17beta-estradiol-D-17beta-glucuronide (E217betaG), vincristine, and doxorubicin across the BBB of mrp1(-/-) and wild-type mice was evaluated by in situ brain perfusion [15].
• We examined the developmental appearance of MRP using immunofluorescence microscopy and found MRP localized in the mouse placenta between days 9 and 13 of development [16].

References