Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer

Lizhi Zhang, Li Chenwei, Redah Mahmood, Kenneth Van Golen, Joel Greenson, Gangyong Li, Nisha J. D'Silva, Xiangquan Li, Charles F. Burant, Craig D. Logsdon, Diane M. Simeone

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Human chromosome 1p35-p36 has long been suspected to harbor a tumor suppressor gene in pancreatic cancer and other tumors. We found that expression of rap1GAP, a gene located in this chromosomal region, is significantly down-regulated in pancreatic cancer. Only a small percentage of preneoplastic pancreatic intraductal neoplasia lesions lost rap1GAP expression, whereas loss of rap1GAP expression occurred in 60% of invasive pancreatic cancers, suggesting that rap1GAP contributes to pancreatic cancer progression. In vitro and in vivo studies showed that loss of rap1GAP promotes pancreatic cancer growth, survival, and invasion, and may function through modulation of integrin activity. Furthermore, we showed a high frequency of loss of heterozygosity of rap1GAP in pancreatic cancer. Collectively, our data identify rap1GAP as a putative tumor suppressor gene in pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)898-906
Number of pages9
JournalCancer research
Volume66
Issue number2
DOIs
StatePublished - Jan 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Zhang, L., Chenwei, L., Mahmood, R., Van Golen, K., Greenson, J., Li, G., D'Silva, N. J., Li, X., Burant, C. F., Logsdon, C. D., & Simeone, D. M. (2006). Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer. Cancer research, 66(2), 898-906. https://doi.org/10.1158/0008-5472.CAN-05-3025