Mammary epithelial-specific expression of the integrin linked kinase (ILK)results in the induction of mammary gland hyperplasias and tumors in transgenic mice

Citation
De. White et al., Mammary epithelial-specific expression of the integrin linked kinase (ILK)results in the induction of mammary gland hyperplasias and tumors in transgenic mice, ONCOGENE, 20(48), 2001, pp. 7064-7072
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
20
Issue
48
Year of publication
2001
Pages
7064 - 7072
Database
ISI
SICI code
0950-9232(20011025)20:48<7064:MEEOTI>2.0.ZU;2-S
Abstract
The integrin linked kinase (ILK) is a cytoplasmic effector of integrin rece ptors, involved in the regulation of integrin binding properties as well as the activation of cell survival and proliferative pathways, including thos e involving MAP kinase, PKB/Akt and GSK-3 beta. Overexpression of ILK in cu ltured intestinal and mammary epithelial cells has been previously shown to induce changes characteristic of oncogenic transformation, including ancho rage-independent growth, invasiveness, suppression of anoikis and tumorigen icity in nude mice. In order to determine if ILK overexpression can result in the formation of mammary tumors in vivo, we generated transgenic mice ex pressing ILK in the mammary epithelium, under the transcriptional control o f the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). By the a ge of 6 months, female MMTV/ILK mice developed a hyperplastic mammary pheno type, which was accompanied by the constitutive phosphorylation of PKB/Akt, GSK-3 beta and MAP kinase. Focal mammary tumors subsequently appeared in 3 4% of the animals at an average age of 18 months. Given the focal nature an d long latency of the tumors, however, additional genetic events are likely required for tumor induction in the MMTV/ILK mice. These results provide t he first direct demonstration of a potential oncogenic role for ILK, which is upregulated in human tumors and tumor cell lines.