Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer.
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.
Zhang
Lizhi
L
Department of Surgery, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
Chenwei
Li
L
Mahmood
Redah
R
van Golen
Kenneth
K
Greenson
Joel
J
Li
Gangyong
G
D'Silva
Nisha J
NJ
Li
Xiangquan
X
Burant
Charles F
CF
Logsdon
Craig D
CD
Simeone
Diane M
DM
D002470:Cell Survival; D018450:Disease Progression; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D016023:Integrins / Q000378:metabolism; D019656:Loss of Heterozygosity; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology
D020690:GTPase-Activating Proteins; D016023:Integrins; C484658:RAP1GAP protein, human