WISP3 is a novel tumor suppressor gene of inflammatory breast cancer

Celina G. Kleer, Yanhong Zhang, Quintin Pan, Kenneth L. Van Golen, Zhi Fen Wu, D. Livant, Sofia D. Merajver

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a 5-year disease-free survival of less than 45%. Little is known about the genetic alterations that result in IBC. In our previous work, we found that WISP3 was specifically lost in human IBC tumors when compared to stage-matched, non-IBC tumors. We hypothesize that WISP3 has tumor suppressor function in the breast and that it may be a key genetic alteration that contributes to the unique IBC phenotype. The full-length WISP3 cDNA was sequenced and cloned into an expression vector. The resulting construct was introduced in to the SUM149 cell line that was derived from a patient with IBC and lacks WISP3 expression. In soft agar, stable WISP3 transfectants formed significantly fewer colonies than the controls. Stable WISP3 transfectants lost their ability to invade and had reduced angiogenic potential. WISP3 transfection was effective in suppressing in vivo tumor growth in nude mice. Mice bearing WISP3 expressing tumors had a significantly longer survival than those with vector-control transfectant tumors. Our data demonstrate that WISP3 acts as a tumor suppressor gene in the breast. Loss of WISP3 expression contributes to the phenotype of IBC by regulating tumor cell growth, invasion and angiogenesis.

Original languageEnglish (US)
Pages (from-to)3172-3180
Number of pages9
JournalOncogene
Volume21
Issue number20
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Inflammatory Breast Neoplasms
Tumor Suppressor Genes
Breast Neoplasms
Neoplasms
Breast
Phenotype
Growth
Nude Mice
Disease-Free Survival
Agar
Transfection
Complementary DNA
Cell Line
Survival

Keywords

  • Angiogenesis
  • Breast cancer
  • Tumor suppressor gene
  • WISP3

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Kleer, C. G., Zhang, Y., Pan, Q., Van Golen, K. L., Wu, Z. F., Livant, D., & Merajver, S. D. (2002). WISP3 is a novel tumor suppressor gene of inflammatory breast cancer. Oncogene, 21(20), 3172-3180. https://doi.org/10.1038/sj.onc.1205462

WISP3 is a novel tumor suppressor gene of inflammatory breast cancer. / Kleer, Celina G.; Zhang, Yanhong; Pan, Quintin; Van Golen, Kenneth L.; Wu, Zhi Fen; Livant, D.; Merajver, Sofia D.

In: Oncogene, Vol. 21, No. 20, 01.01.2002, p. 3172-3180.

Research output: Contribution to journalArticle

Kleer, CG, Zhang, Y, Pan, Q, Van Golen, KL, Wu, ZF, Livant, D & Merajver, SD 2002, 'WISP3 is a novel tumor suppressor gene of inflammatory breast cancer', Oncogene, vol. 21, no. 20, pp. 3172-3180. https://doi.org/10.1038/sj.onc.1205462
Kleer CG, Zhang Y, Pan Q, Van Golen KL, Wu ZF, Livant D et al. WISP3 is a novel tumor suppressor gene of inflammatory breast cancer. Oncogene. 2002 Jan 1;21(20):3172-3180. https://doi.org/10.1038/sj.onc.1205462
Kleer, Celina G. ; Zhang, Yanhong ; Pan, Quintin ; Van Golen, Kenneth L. ; Wu, Zhi Fen ; Livant, D. ; Merajver, Sofia D. / WISP3 is a novel tumor suppressor gene of inflammatory breast cancer. In: Oncogene. 2002 ; Vol. 21, No. 20. pp. 3172-3180.
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