Wasf3 Deficiency Reveals Involvement in Metastasis in a Mouse Model of Breast Cancer

Haiyan Qin, Sumin Lu, Muthusamy Thangaraju, John K. Cowell

Research output: Contribution to journalArticle

Abstract

The WASF3 gene has been implicated in cancer cell movement, invasion, and metastasis by regulating genetic pathways important in these processes. Invasion and metastasis assays, however, are largely centered on xenograft models in immune-compromised mice. To facilitate analysis of the role of WASF3 in the spontaneous development of cancer cell metastasis, we generated a Wasf3 null strain by deleting exons 4 and 5, which encode essential motifs for Wasf3 function. On exposure to cre-recombinase a stop codon is generated immediately downstream in exon 6. Using a cytomegalovirus (CMV)-cre strain, Wasf3 constitutively was inactivated, which led to viable mice with no visible morphologic or behavioral abnormalities. There was no abnormal development or function of the mouse mammary gland in the Wasf3 null mice and brain development was normal. In the mouse mammary tumor virus (MMTV)-driven polyoma middle-T oncogene strain, which shows early onset breast cancer development and metastasis, Wiskott-Aldrich syndrome protein family member 3 (Wasf3) is up-regulated in metastatic lesions. When this oncogene was introduced onto the Wasf3-null background, although metastasis was observed in these mice, there was a reduction in the number and size of metastatic lesions in the lungs. These data provide evidence for a role in WASF3 in the development of metastasis in a spontaneous model of breast cancer.

Original languageEnglish (US)
Pages (from-to)2450-2458
Number of pages9
JournalAmerican Journal of Pathology
Volume189
Issue number12
DOIs
StatePublished - Dec 2019

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Wiskott-Aldrich Syndrome Protein Family
Breast Neoplasms
Neoplasm Metastasis
Oncogenes
Exons
Mouse mammary tumor virus
Terminator Codon
Human Mammary Glands
Cytomegalovirus
Heterografts
Cell Movement
Neoplasms
Lung
Brain

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Wasf3 Deficiency Reveals Involvement in Metastasis in a Mouse Model of Breast Cancer. / Qin, Haiyan; Lu, Sumin; Thangaraju, Muthusamy; Cowell, John K.

In: American Journal of Pathology, Vol. 189, No. 12, 12.2019, p. 2450-2458.

Research output: Contribution to journalArticle

Qin, Haiyan ; Lu, Sumin ; Thangaraju, Muthusamy ; Cowell, John K. / Wasf3 Deficiency Reveals Involvement in Metastasis in a Mouse Model of Breast Cancer. In: American Journal of Pathology. 2019 ; Vol. 189, No. 12. pp. 2450-2458.
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