An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity

Recent evidence indicates that the estrogen receptor-a-negative, androgen receptor (AR)- positive molecular apocrine subtype of breast cancer is driven by AR signaling. The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype; its proliferation is stimulated by androgens such as 5a-dihydrotestosterone (DHT) but inhibited by the progestin medroxyprogesterone acetate (MPA) via AR-mediated mechanisms. We report here that the AR gene in MDAMB- 453 cells contains a G-T transversion in exon 7, resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 (Q865H) in the ligand binding domain. Compared with wild-type AR, the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists. Ligand binding, molecular modeling, mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation, AR intramolecular interactions, and receptor stability. Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells. Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway. These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant. This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype. Endocrine-Related Cancer (2012) 19 599–613

MP 453, de 2009 : emendas

Consultoria Legislativa - Área IV - Finanças Públicas.

Ciclo I de seleção na população de milho CMS 453 nos tabuleiros costeiros do nordeste brasileiro.

1998

Ciclo II de seleção entre e dentro de progênies de meios-irmãos na população de milho CMS 453.

1998

Ciclo III de seleção entre e dentro de progênies de meios irmãos na população de milho CMS-453.

1999

Evaluation of quality of life over time among 453 patients with hyperhidrosis submitted to endoscopic thoracic sympathectomy

Objectives: Current data do not provide enough information on how quality of life (QoL) evolves over time in cases of endoscopic thoracic sympathectomy (ETS). The purpose of this study was to ascertain whether the immediate improvement in QoL after the surgery was sustained until the fifth postoperative year. Methods: This was a prospective, nonrandomized and uncontrolled study. From March 2001 to December 2003, 475 consecutive patients with hyperhidrosis submitted to ETS were included. A QoL questionnaire was applied at the preoperative day, around the 30th postoperative day, and after the fifth year. Results: After excluding 22 patients who did not answer all the questions, we analyzed 453 patients. Their ages ranged from 11 to 57 years old, with a mean of 25.3 + 7.9 years, including 297 female patients (65.6%). All patients were assessed on three occasions: before surgery, around the 30th postoperative day, and after the fifth postoperative year. The QoL before surgery was considered to be poor or very poor for all patients. The QoL around 30 days after surgery was better in 412 patients (90.9%), the same in 27 patients (6.0%), and worse in 14 patients (3.1%). After 5 years, 409 patients (90.3%) were better, 27 (6.0%) were the same, and 14 (3.1%) were worse. There were no differences between these postoperative times according to the McNemar statistical test. Conclusion:The patients had an immediate improvement in QoL after ETS, and this improvement was sustained until the fifth postoperative year. (J Vase Surg 2012;55:154-6.)

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 453 - Ergänzung für die 3. Auflage der "Welt als Wille und Vorstellung"

u.a.: Problem der Päderastie, griechische Klassiker;

Na 1 Nachlass Max Horkheimer, 60 - Korrespondenzen u.a. mit der American Friends Service Committee (p. II 1, 226-453)

1 Brief von Max Horkheimer an die Commerzbank Stuttgart, 1947; 2 Briefe von Max Horkheimer an die United States Lines, 1946-1947; 4 Brief und Beilage von Max Horkheimer an das American Consulate General Stuttgart, 1940-1941, 1946; 1 Brief von Max Horkheimer an das Hebrew Sheltering and Immigrant Aid, 1946; 1 Brief von Max Horkheimer an Lilly Straus, 1945; 2 Briefe von Max Horkheimer an Herbert S. Eskin, 1945; 3 Briefe von Max Horkheimer an State of New York, 1939-1941; 5 Briefe von Max Horkheimer an das American Friends Service Committee, 1940-1941; 2 Briefe von Max Horkheimer an Elisabeth Kunz, 1941;