Familial history is the strongest risk factor for developing ovarian cancer (OC), and a significant contributor to breast cancer risk. Most hereditary breast cancers and OCs are associated with mutation of the tumor suppressor Breast and Ovarian Cancer Susceptibility Gene 1 (BRCA1). Studying risk-associated BRCA1 truncation mutations, such as the founder mutation 185delAG, may reveal signaling pathways important in OC etiology. Recent studies have shown novel BRCA1 mutant functions that may contribute to breast and OC initiation and progression independent of the loss of wtBRCA1. Previously, we have found that normal human ovarian surface epithelial (HOSE) cells expressing the 185delAG mutant, BRAT ( BRCA1 185delAG Amino Terminal truncated protein), exhibit enhanced chemosensitivity and up-regulation of the OC-associated serpin, maspin. In the current study, I identify an additional target of the BRAT mutation, matrix metalloprotease 1 (MMP1), a key player in invasion and metastasis. BRAT-expressing HOSE cells exhibit increased MMP1 messenger RNA (mRNA) by real time PCR and protein by Western blotting. Pro-MMP1 levels are also higher in conditioned media of BRAT-expressing cells and HOSE cell lines derived from BRAT mutation carriers. c-Jun is critical for BRAT-mediated MMP1 up-regulation, as siRNA knockdown diminishes MMP1 levels. Luciferase reporter constructs reveal that activator Protein 1 (AP1) sites throughout the distal end of the promoter contribute to BRAT-mediated MMP1 expression, and basal activity is mediated in part by an AP1 site at (-72). Reporters containing a single nucleotide polymorphism (SNP) associated with OC risk and progression yield increased activity that is further enhanced in BRAT cells. Interestingly, BRAT-mediated changes in chemosensitivity and gene regulation are not recapitulated in a normal breast epithelial or breast cancer cell model. This suggests tissue-specific mutant BRCA1 functions may contribute to breast and ovarian tissue specificity of BRCA1 mutation-associated cancer risk and also to differential breast and ovarian cancer risk and penetrance associated with specific mutations. Early molecular and cellular changes such as MMP1 up-regulation in the ovarian surface epithelium of BRCA1 mutation carriers may promote OC initiation and progression and represent a step forward on the continuum of cellular malignancy. Further investigation is warranted, as elucidating these early changes will aid in identification of potential screening and treatment strategies.

abstract: American families have been coming to South Korea accompanying active duty service members or Embassy employees since before the Korean War. While their numbers were originally smaller, they continue to increase as South Korean assignments undergo "tour normalization", a transition from a location intended for service members to come alone for one year to a location where service members come accompanied by their family and stay for longer periods of times. The U.S. maintains a large presence in South Korea as a deterrence against possible threats from North Korea. Despite establishment of an armistice at the conclusion of the Korean War, a constant state of potential threat was created. This paper will examine what affect the recent rise in tension between North Korea and South Korea has on the American children living in South Korea with their active duty service member parent(s). / Dissertation/Thesis / M.A. Social and Philosophical Foundations of Education 2012

L'objectif de cette thèse est d'étudier trois romans écrits par des auteurs anglophones du Pakistan ou de l'Inde, à savoir Bapsi Sidhwa, Bharati Mukherjee et Hanif Kureishi. On pourrait être tenté de placer les trois écrivains de cette étude dans la catégorie «littérature des immigrants». Ils écrivent tous à un moment de migration de masse lorsque l'idée de «choc culturel» parmi les peuples occidentaux commence à être plus évidente. Les trois écrivains sont affectés par des thèmes qui apparaissent seulement de manière marginale dans le débat évoqué ci-dessus, l'accent étant principalement mis sur les difficultés culturelles et sociales des femmes dans la société indo-pakistanaise. Quant à Kureishi, la polarisation mentionnée ci-dessus suppose un accent très différent, impliquant la situation d'un Asiatique né et élevé dans la société occidentale. Dans cette évaluation globale du contexte idéologique et historique commun aux trois écrivains, il sera important d'examiner les attitudes spécifiques adoptées par chaque écrivain par rapport à son expérience personnelle. L'objectif principal de cette étude sera donc thématique, en se concentrant sur les préoccupations spécifiques de ces écrivains et sur la manière dont cela se manifeste dans leur représentation particulière des tensions en jeu. / The objective of this thesis is to study three novels written by English-speaking authors of Pakistan or India, namely Bapsi Sidhwa, Bharati Mukherjee and Hanif Kureishi. One might be tempted to place the three writers of this study in the category of "literature of immigrants." They all write at a time of mass migration when the idea of "cultural shock" among Western peoples begins to be more evident. All three writers are affected by themes which appear only marginally in the debate evoked above, much of the emphasis being on the cultural and social difficulties of women in Indo-Pakistani society. As for Kureishi, the polarization mentioned above assumes a very different emphasis, involving the situation of an Asian born and brought up inside Western society. Within this overall assessment of the ideological and historical context common to all three writers, it will thus be important to examine the specific attitudes adopted by each writer in relation to his or her own personal experience. The main focus of this study will therefore be thematic, centering on these writers’ specific preoccupations and the way this is seen in their peculiar depiction of the tensions at stake.

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