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

Donald E. White, Robert Cardiff, Shoukat Dedhar, William J. Muller

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

The integrin linked kinase (ILK) is a cytoplasmic effector of integrin receptors, involved in the regulation of integrin binding properties as well as the activation of cell survival and proliferative pathways, including those involving MAP kinase, PKB/Akt and GSK-3β. Over-expression of ILK in cultured intestinal and mammary epithelial cells has been previously shown to induce changes characteristic of oncogenic transformation, including anchorage-independent growth, invasiveness, suppression of anoikis and tumorigenicity in nude mice. In order to determine if ILK overexpression can result in the formation of mammary tumors in vivo, we generated transgenic mice expressing ILK in the mammary epithelium, under the transcriptional control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). By the age of 6 months, female MMTV/ILK mice developed a hyperplastic mammary phenotype, which was accompanied by the constitutive phosphorylation of PKB/Akt, GSK-3β and MAP kinase. Focal mammary tumors subsequently appeared in 34% of the animals at an average age of 18 months. Given the focal nature and long latency of the tumors, however, additional genetic events are likely required for tumor induction in the MMTV/ILK mice. These results provide the first direct demonstration of a potential oncogenic role for ILK, which is upregulated in human tumors and tumor cell lines.

Original languageEnglish (US)
Pages (from-to)7064-7072
Number of pages9
JournalOncogene
Volume20
Issue number48
DOIs
StatePublished - Oct 25 2001

Fingerprint

Human Mammary Glands
Transgenic Mice
Hyperplasia
Breast
Breast Neoplasms
Mouse mammary tumor virus
Glycogen Synthase Kinase 3
Integrins
Phosphotransferases
Anoikis
Neoplasms
Terminal Repeat Sequences
integrin-linked kinase
Tumor Cell Line
Nude Mice
Cell Survival
Epithelium
Epithelial Cells
Phosphorylation
Phenotype

Keywords

  • Breast cancer
  • ILK
  • Integrin linked kinase
  • Mammar epithelium
  • Transgenic mice
  • Tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Mammary epithelial-specific expression of the integrin linked kinase (ILK) results in the induction of mammary gland hyperplasias and tumors in transgenic mice. / White, Donald E.; Cardiff, Robert; Dedhar, Shoukat; Muller, William J.

In: Oncogene, Vol. 20, No. 48, 25.10.2001, p. 7064-7072.

Research output: Contribution to journalArticle

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