Étude de la régulation de l'expression de PAX-5 et de ses isoformes dans le cancer du sein: implication des récepteurs d'oestrogène ERα et ERβ 3

Breast cancer is the most common type of cancer affecting women worldwide. Estrogen receptors ERα and ERβ are ligand-dependent transcriptional factors that mediate oestrogens biological effects, namely those of 17β-estradiol. They are expressed in the most cases of breast cancer and are well characterized for their role in the initiation and progression of this type of cancer. Pax-5 is another transcription factor which plays a crucial role in B lymphopoiesis and whose deregulation has been associated to certain malignancies, namely non-Hodgkin lymphomas and acute lymphoblastic leukemia. Although Pax-5 is known to be expressed mainly in B cells, the brain during development and to a lesser extent in lungs and adult testis, recent findings suggest its expression in some breast cancer cell lines and primary breast tumors. Moreover, we found a number of estrogen receptor binding sites on the Pax-5 promoter and it's been shown that Pax-2, a member of the same subfamily as Pax-5, is regulated by ERα in cancerous endometrial epithelial cells. Hence, we formulated the hypothesis that Pax-5 is a target gene of estrogen receptors in breast cancer. In order to better characterize Pax-5 expression patterns in breast cancer, immunofluorescence and immunohistochemistry assays were performed on cancerous and normal breast cells lines as well as various breast tumors. We also performed electrophoretic mobility shift assays to assess the binding capacity of estrogen receptors ERα and ERβ on those predicted sites and subsequently evaluated the receptors activity by dual luciferase reporter assays. We report here the expression of Pax-5 isoforms in the ER-positive breast cancer line MCF-7 but not in the non-malignant ER-negative breast cell line MCF-10A or the malignant breast cell line MDA-MB-231. Pax-5 expression was also observed in a large subset of the primary breast tumors studied, which correlated with the presence of ERs in these tissues. We also show that ERs bind to all of the ER elements located on the Pax-5 promoter and stimulate its activity under 17β-estradiol and Tamoxifen treatment. Taken together, these results provide the first strong evidence for the direct influence of estrogen receptors on the expression of Pax-5 in breast cancer and suggest a mechanism by which this oncogene contributes to breast carcinogenesis.

Name thesis:degree_name

Maîtrise ès sciences (biochimie)

Level thesis:degree_level

2e cycle

Discipline thesis:degree_discipline

Faculté des sciences

Grantor dc:publisher

Université de Moncton

Year dc:date.issued

2010

Author dc:creator

• Faye, Mame Daro

Advisor dc:contributor.advisor

• Ouellette, Rodney

• Œstrogènes
• Récepteurs
• Facteurs de transcription
• Promoteurs (Chimie)
• Sein
• Cancer

Statement dc:rights

• Author

Language dc:language.iso

iso639-2b, fre

Identifier

oclc: 769771473
oclc: 910405690

Dc Identifier Other

umir:1526

OAI identifier oai:identifier

oai:umoncton.scholaris.ca:20.500.14658/7999