Phosphatase and tensin homologue deleted on chromosome 10 deficiency accelerates tumor induction in a mouse model of ErbB-2 mammary tumorigenesis

Nathalie Dourdin, Babette Schade, Robert Lesurf, Michael Hallett, Robert J. Munn, Robert Cardiff, William J. Muller

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Abstract

Loss of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and amplification or elevated expression of ErbB-2 are both involved in human breast cancer. To directly test the importance of these genetic events in mammary tumorigenesis, we have assessed whether mammary-specific disruption of PTEN could cooperate with activation of ErbB-2. Transgenic mice expressing ErbB-2 under the transcriptional control of its endogenous promoter (ErbB-2KI) were interbred with mice carrying conditional PTEN alleles and an MMTV/Cre transgene. Loss of one or both PTEN alleles resulted in a dramatic acceleration of mammary tumor onset and an increased occurrence of lung metastases in the ErbB-2KI strain. Tumor progression in PTEN-deficient/ErbB-2KI strains was associated with elevated ErbB-2 protein levels, which were not due to ErbB-2 amplification or to a dramatic increase in ErbB-2 transcripts. Moreover, the PTEN-deficient/ErbB- 2KI-derived mouse mammary tumors display striking morphologic heterogeneity in comparison with the homogeneous pathology of the ErbB-2 KI parental strain. Therefore, inactivation of PTEN would not only have a dramatic effect on ErbB-2-induced mammary tumorigenesis but would also lead to the formation of mammary tumors that, in part, display pathologic and molecular features associated with the basal-like subtype of primary human breast cancer.

Original languageEnglish (US)
Pages (from-to)2122-2131
Number of pages10
JournalCancer Research
Volume68
Issue number7
DOIs
StatePublished - Apr 1 2008

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Chromosomes, Human, Pair 10
Phosphoric Monoester Hydrolases
Carcinogenesis
Breast
Breast Neoplasms
Neoplasms
Alleles
Transgenes
Transgenic Mice
Tensins
Pathology
Neoplasm Metastasis
Lung
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Phosphatase and tensin homologue deleted on chromosome 10 deficiency accelerates tumor induction in a mouse model of ErbB-2 mammary tumorigenesis. / Dourdin, Nathalie; Schade, Babette; Lesurf, Robert; Hallett, Michael; Munn, Robert J.; Cardiff, Robert; Muller, William J.

In: Cancer Research, Vol. 68, No. 7, 01.04.2008, p. 2122-2131.

Research output: Contribution to journalArticle

Dourdin, Nathalie ; Schade, Babette ; Lesurf, Robert ; Hallett, Michael ; Munn, Robert J. ; Cardiff, Robert ; Muller, William J. / Phosphatase and tensin homologue deleted on chromosome 10 deficiency accelerates tumor induction in a mouse model of ErbB-2 mammary tumorigenesis. In: Cancer Research. 2008 ; Vol. 68, No. 7. pp. 2122-2131.
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