Tissue specific promoters

Details Tissue specific promoters Tissue specific promoters

C - Chemistry, Metallurgy

12

N

C12N 5/00 (2006.01) A61K 49/00 (2006.01) C07H 21/02 (2006.01) C07H 21/04 (2006.01) C07K 14/47 (2006.01) C12N 15/00 (2006.01) C12N 15/85 (2006.01)

Patent

CA 2285413

The present invention provides human involucrin (hINV) sequences having tissue specific and cell type specific promoter activity. The sequences provided herein direct expression to suprabasal cells of stratifying epithelia. The invention further provides transgenic animals which contain an hINV promoter sequence which directs the expression of human papillomavirus 16 oncogenes. These animals display cervical and epidermal hyperplasias as well as cancer of the trachea, esophagus, colon, epidermis, anus/rectum, lymph nodes, spleen and lung. The animals of the invention provide a useful model for screening potential anti-neoplastic compounds, carcinogens, and co-carcinogens for a number of cancers.

Cette invention a trait à des séquences d'involucrine humaine (hINV) faisant preuve d'une activité de promoteur à spécificité tissulaire et cellulaire. Les séquences de l'invention dirigent l'expression sur des cellules suprabasales d'épithélium à stratification. L'invention concerne également des animaux transgéniques renfermant une séquence de promoteur d'hINV dirigeant l'expression d'oncogènes de papillomavirus humain 16. Ces animaux présentent des hyperplasies cervicales et épidermiques ainsi que des cancers de la trachée, de l'oesophage, du colon, de l'épiderme, de l'anus et/ou du rectum, des ganglions lymphatiques ainsi que de la rate et du poumon. Les animaux de l'invention constituent un modèle utile en matière de criblages de composés antinéoplasiques potentiels, de substances cancérogènes et co-cancérogènes, criblages portant sur un certain nombre de cancers.

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