Estrogen receptor (ER) a plays an important role in the proliferation and progression of breast cancer. In order to explore the function of wild-type ERb (ERb1) and its variant form, ERbcx/b2, stable transformants of ERapositive breast cancer MCF7 cells with ERb1 or ERbcx/ b2 expression vector were established. Constitutive expression of ERb1 or ERbcx/b2 reduced the S phase population of the cell cycle in dish culture and the number of colonies in an anchorage-independent assay. DNAprotein complexes of ERE with nuclear extracts from ERb1 transformants were observed in the electrophoretic mobility shift assay, while no complex was observed for ERbcx/b2 transformants. Reporter gene assay using estrogen-responsive element (ERE)-luciferase showed less responsiveness to estrogen in these transformants compared with parental cells. Endogenous mRNA expression of two known estrogen-responsive genes, cathepsin D and IGFBP4, was weakly induced by estrogen in ERb1 and ERbcx/b2 transformants compared with parental cells. A comprehensive gene expression analysis using our custommade cDNA microarray showed that MCF7 and ERb1 transformants had a similar gene expression profile, whereas ERbcx/b2 showed a distinct profile from others. These results indicate that ERb1 and ERbcx/b2 inhibit ERa function differently in MCF7 cells.

A factor inducing differentiation of mouse myeloid leukemic cells (M1) into macrophages was purified to apparent homogeneity from 168 1 of CM of Ehrlich ascites tumor cells. The purified factor was halt‐maximally active at 2 × 10−11 M. The factor was analyzed by radioiodination, SDS‐polyacrylamide gel electrophoresis and autoradiography. Its M r was 40000–50000. On reduction, the factor lost activity, but showed no subunit structure. Treatment of the factor with endo‐β‐N‐acetylglucosaminidase F, but not endo‐β‐N‐acetylglucosaminidase H, gave rise to a molecule of M r 20000–28000. The activity of the factor from Ehrlich cells was completely neutralized by antiserum to the factor of M r 50000–70000 from mouse fibroblast L929 cells.

Vesnarinone, an oral cardiotonic, inhibited the growth of several human non-small cell lung carcinoma cell lines, and its anti-proliferative effects in vitro and in vivo were greatly enhanced by combination with glucocorticoids, but not other steroids. Simultaneous treatment with vesnarinone and dexamethasone is the most effective to evoke the synergistic effect in the growth inhibition of lung carcinoma EBC-1 cells. Dexamethasone and other glucocorticoids induced morphological changes in EBC-1 cells and these agents together with vesnarinone induced alkaline phosphatase activity, which is a typical marker of type II pneumocyte maturation. This treatment arrested the growth of the cells at the G 1 phase, indicating that this treatment is cytostatic rather than cytotoxic. These results suggest that vesnarinone plus glucocorticoid might be useful in lung cancer therapy. © 1999 Cancer Research Campaign

Three cDNAs for mouse differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) receptor were isolated from a cDNA library prepared from the liver of a pregnant mouse. A probe for screening was prepared by the RT-PCR method using human cDNA sequences as primers. The mouse D-factor receptor cDNA encoded 1,092 amino acids, which had a marked homology with the human counterpart and consisted of signal sequence, extracellular, transmembrane, and cytoplasmic domains. The WSXWS motif found in members of the cytokine receptor family was also present in the extracellular domain of the mouse D-factor receptor. A second form of cDNA that had a 501 bp insertion was isolated. The insertion introduced a stop codon so that the mRNA encoded the soluble receptor lacking transmembrane and intracellular domains. Because the insertion contained polyadenylation signals, two different sizes of mRNA encoding the soluble receptor were produced, depending on whether or not it utilized these signals. Transcripts utilizing these signals were 2.6-3 kb in size, and were very abundantly expressed in the liver. Transcripts that did not use these signals were longer than 5 kb and of similar size to the mRNA for the cellular receptor.

The outcome of patients with non-Hodgkin’s lymphoma has been improved by current approaches to treatment. Nevertheless, many patients either do not have a complete remission or ultimately relapse. To identify such patients, it is important to be able to predict the outcome. We previously found that the differentiation inhibitory factor/nm23 was correlated with the prognosis of acute myeloid leukemia. To examine the prognostic effect of nm23 on non-Hodgkin’s lymphoma, we established an enzyme-linked immunosorbent assay procedure to determine nm23-H1 protein levels in plasma and assessed the association of this protein level with the response to chemotherapy, overall survival, and progression-free survival in patients with aggressive non-Hodgkin’s lymphoma. The plasma concentration of nm23-H1 was significantly higher in patients with malignant lymphoma than in normal controls, especially in aggressive non-Hodgkin’s lymphoma. The complete remission rate in patients with higher nm23-H1 levels was significantly worse than that in patients with lower nm23-H1 levels. Overall survival and progression-free survival were also lower in patients with higher nm23-H1 levels than in those with lower levels. The 3-year survival rates in patients with low and high nm23-H1levels were 79.5% and 6.7% (P = .0001). A multivariate analysis of prognostic factors showed that the plasma nm23-H1level was independently associated with the survival and progression-free survival. An elevated plasma nm23-H1concentration predicts a poor outcome of advanced non-Hodgkin’s lymphoma. Therefore, nm23-H1 in plasma may be useful for identifying a distinct group of patients at very high risk.