Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Context: A functional vacuolar adenosine triphosphatase (v-ATPase) complex regulates canonical Wnt/β-catenin signaling. The goal of this study was to identify the distribution of the v-ATPase in human and murine models of pancreatic intraepithelial neoplasms (PanINs) and assess its role in Wnt/β-catenin signaling.', 'We evaluated the immunolabeling pattern of the v-ATPase in human PanIN specimens and murine PanIN-1 and PanIN-2 lesions obtained from Ptf1a(Cre/+); LSL-Kras(G12D) mice. Wnt/β-catenin signaling was interrogated in primary PanIN cells by examining the phosphorylated levels of its surface coreceptor, low-density lipoprotein receptor-related protein-6 (LRP6), and its intracellular effector, nonphosphorylated β-catenin. The response of primary PanIN cells to epidermal growth factor (EGF) was assessed in the absence and presence of the v-ATPase inhibitor, concanamycin.', 'In advanced (PanIN-2), but not early (PanIN-1), lesions, the v-ATPase assumed a polarized phenotype. Blocking the v-ATPase disrupted Wnt/β-catenin signaling in primary PanIN cells despite significantly higher levels of the total and activated Wnt cell surface coreceptor, LRP6. Vacuolar adenosine triphosphatase blockade significantly decreased the total and activated levels of EGF receptor, a determinant of PanIN progression. The activation of EGF receptor and its intracellular mediator, p44/42 mitogen-activated protein kinase, was also reduced by v-ATPase blockade. This led to diminished proliferation in response to EGF ligand.
Answer: The v-ATPase regulates Wnt/β-catenin and EGF receptor signaling in PanINs.
Does polarization of the vacuolar adenosine triphosphatase delineate a transition to high-grade pancreatic intraepithelial neoplasm lesions?

Context: Recently we have shown that the imunoglobulins G from blood serum of some multiple sclerosis patients are capable of cleaving histone H1.', 'To check whether histone H1-hydrolyzing abzymes could be detected not only in blood plasma of autoimmune patients, but also during cancer development, particularly during the onset of multiple myeloma.', "Immunoglobulines were isolated from blood serum of multiple myeloma patients (n = 11) by precipitation with 50% ammonium sulfate and tested for proteolytic activity toward linker and core calf thymus histones. Antibody preparations able to cleaved histone H1 were subjected to affinity chromatography on histone H1-Sepharose with following analysis of chromatographic fractions' protease activity. To prove that antibody molecules are responsible for hydrolysis of histone H1, gel filtration at acidic pH with subsequent examination of protease activity of chromatographic fractions (pH-shock analysis) was used.", 'It was found that 3 of 11 antibody preparations are capable of hydrolyzing calf thymus histone H1 but not core histones. It was shown that histone H1-hydrolysing activity of 2 proteolytically active antibody preparations is associated with IgGs that possess affinity towards histone H1. pH-shock analysis proved that protease activity towards histone H1 is intrinsic property of IgG molecules.
Answer: We demonstrated the existence of previously unknown histone H1 hydrolyzing IgG abzymes in the serum of multiple myeloma patients. Possible biological role of hisH1-hydrolyzing antibodies in patients with multiple myeloma was discussed.
Are blood serum immunoglobulins of patients with multiple myeloma capable of hydrolysing histone H1?

Context: During early to late-fetal liver development, bipotential hepatoblasts proliferate and differentiate into hepatocytes and cholangiocytes. The prospero-related homeobox 1 gene (Prox1) is expressed in hepatoblasts, and the inactivation of Prox1 causes defective early liver development, in particular, faulty migration of fetal hepatoblasts. Prox1 binds to another hepatocyte-enriched transcription factor, liver receptor homolog 1 (Lrh1), and suppresses its transcriptional activity. However, the molecular mechanism by which Prox1 and Lrh1 regulate the characteristics of fetal hepatic cells remains unknown. We investigated the contribution of Prox1 and Lrh1 in early liver development. Embryonic day 13 liver-derived CD45-Ter119-Dlk+ cells were purified as fetal hepatic stem/progenitor cells, and formation of colonies derived from single cells was detected under low-density culture conditions. We found that overexpression of Prox1 using retrovirus infection induced migration and proliferation of fetal hepatic stem/progenitor cells. In contrast, overexpression of Lrh1 suppressed colony formation. Prox1 induced the long-term proliferation of fetal hepatic stem/progenitor cells, which exhibited both high proliferative activity and bipotency for differentiation. Prox1 up-regulated expression of cyclins D2, E1, and E2, whereas it suppressed expression of p16(ink4a), the cdk inhibitor. In addition, overexpression of Prox1 significantly inhibited the proximal promoter activity of p16(ink4a).
Answer: These results suggested that Prox1 and Lrh1 coordinately regulate development of hepatic stem/progenitor cells and that Prox1 induces fetal hepatocytic proliferation through the suppression of the promoter activity of p16(ink4a).

Do prospero-related homeobox 1 and liver receptor homolog 1 coordinately regulate long-term proliferation of murine fetal hepatoblasts?