Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer

Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha, at 6q25. A subsequent tissue microarray analysis of more than 2,000 clinical breast cancer samples showed ESR1 amplification in 20.6% of breast cancers. Ninety-nine percent of tumors with ESR1 amplification showed estrogen receptor protein overexpression, compared with 66.6% cancers without ESR1 amplification (P < 0.0001). In 175 women who had received adjuvant tamoxifen monotherapy, survival was significantly longer for women with cancer with ESR1 amplification than for women with estrogen receptor-expressing cancers without ESR1 amplification (P = 0.023). Notably, we also found ESR1 amplification in benign and precancerous breast diseases, suggesting that ESR1 amplification may be a common mechanism in proliferative breast disease and a very early genetic alteration in a large subset of breast cancers.     

Beziehungen zwischen phagozytierenden,virusinfizierten Myeloblasten des Huhnes in vitro und den «gray bodies»

Summary The so-called gray bodies in chicken myeloblasts infected with the myeloblastose virus are phagocytized cell debris. Some difficultues concerning this virus-cell-system are pointed out.

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Die Arbeit wurde unterstützt durch Research grant No. C-4572 an die Duke University von National Cancer Institute, National Institutes of Health, Public Health Service, durch Grant No. E-84A von der American Cancer Society, Inc. und durch den Dorothy Beard Research Fund.     

Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity

Expression of oncogenic Ras in primary human cells activates p53, thereby protecting cells from transformation. We show that in Ras-expressing IMR-90 cells, p53 is phosphorylated at Ser33 and Ser46 by the p38 mitogen-activated protein kinase (MAPK). Activity of p38 MAPK is regulated by the p53-inducible phosphatase PPM1D, creating a potential feedback loop. Expression of oncogenic Ras suppresses PPM1D mRNA induction, leaving p53 phosphorylated at Ser33 and Ser46 and in an active state. Retrovirus-mediated overexpression of PPM1D reduced p53 phosphorylation at these sites, abrogated Ras-induced apoptosis and partially rescued cells from cell-cycle arrest. Inactivation of p38 MAPK (the product of Mapk14) in vivo by gene targeting or by PPM1D overexpression expedited tumor formation after injection of mouse embryo fibroblasts (MEFs) expressing E1A+Ras into nude mice. The gene encoding PPM1D (PPM1D, at 17q22/q23) is amplified in human breast-tumor cell lines and in approximately 11% of primary breast tumors, most of which harbor wildtype p53. These findings suggest that inactivation of the p38 MAPK through PPM1D overexpression resulting from PPM1D amplification contributes to the development of human cancers by suppressing p53 activation.     

Fortuitous discovery of urate nephrolithiasis in rats subjected to portacaval anastomosis

Zusammenfassung Nach Anlage eines portocavalen Shunts bei 53 Sprague-Dawley-Ratten wurde in 47% aller Fälle eine Harnsäure-Urolithiasis beobachtet. Das Vorkommen war bei den Ratten am häufigsten (94%), die mehr als einen Monat überlebten und postoperativ an Gewicht verloren.

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Acknowledgments. The authors are grateful to Dr.K. Lauber of the Department of Medical Chemistry and to Prof.H. Fleisch of the Department of Pathophysiology of the University of Berne for performing the chemical analyses. The technical assistance of MissM. Kappeler and MissB. Schütz is greatly appreciated.     

In vitro biosynthesis of beta-lipotropin in brain tissue]

We have recently developed methods to identify biosynthetized beta-endorphin and beta-lipotropin (beta-LPH) following incubation of Rat pars intermedia with radioactive amino acids. We used the same approach for rat brain tissue. In the striatum we found a peptide similar to beta-LPH while its identification in hypothalamus was less positive. This is the first demonstration of such biosynthesis and it could well be an important step in determining the biosynthetic patterns of cerebral endorphins and enkephalins.     

Thrombozytose und Eosinophilie bei adrenalektomierten Ratten nach einmaliger 5-Hydroxytryptamininjektion

Summary In adrenalectomized rats, the injection of a single high dose of 5-hydroxytryptamin results, as in intact animals previously reported, in a strong increase of the number of platelets in the peripheral blood. The number of eosinophils, instead of decreasing, also rises. The maxima of increase are not in temporal accordance.     

«LH-Releasing-Factor» beim Menschen

Summary There is evidence for LH-releasing-factor (LH-RF) in 18 crude acid extracts of human median eminence preparation following the procedure described byRamirez andMcCann.     

Rosette formation in white blood cell cultures from patients with acute myeloblastic leukemia

Zusammenfassung In Monozyten enthaltenden Leukozyten-Kulturen von Patienten mit akuter myeloischer Leukämie entstehen nach ungefähr 8 h Inkubationszeit Rosetten, die aus einem von Myeloblasten umgebenen Monozyten bestehen. In Analogie zu anderen in vitro-Systemen, in welchen sich eine Rosettenbildung beobachten lässt, könnte diese zelluläre Reaktion auf dem Vorhandensein von spezifischen Antikörpern im Patienten-Serum beruhen, welche gegen die leukämischen Myeloblasten gerichtet sind.