Inactivation of LGI1 expression accompanies early stage hyperplasia of prostate epithelium in the TRAMP murine model of prostate cancer.
The LGI1 gene has been implicated in tumor cell invasion through regulation of the ERK pathway. To determine whether human prostate cancer cells (PC3, 22RV, Du145) are similarly affected by exposure to LGI1, we conducted scratch wound assays and demonstrated that the secreted LGI1 protein can reduce cell motility, an essential component of invasion and metastasis. These studies have now been extended to an in vivo mouse model of prostate cancer. Using a BAC transgenic mouse expressing a GFP reporter gene under the control of cis regulatory elements, we demonstrated that LGI1 is highly expressed in the normal prostate epithelium. To determine whether loss of LGI1 expression is associated with development and progression of murine prostate cancer, we bred the GFP reporter BAC transgenic mice with TRAMP mice which undergo early hyperplasia and progressive stages of prostate cancer. In the F1 animals, although the surrounding normal prostate epithelium expressed high levels of LGI1 in the double transgenic mice, the LGI1 gene had been inactivated even at the earliest stages of hyperplasia. This observation supports the suggestion that inactivation of LGI1 in certain cell types is related to tumor progression. Taken together these results suggest that LGI1 may be an important molecule for the arrest of prostate cancer cell invasion and possibly as a biomarker for early detection of prostate hyperplasia.
MCG Cancer Center, Medical College of Georgia, School of Medicine, 1120 Fifteenth Street, Augusta, GA 30912, USA. jcowell@mcg.edu
John K
JK
Cowell
Karen
K
Head
Padmaja
P
Kunapuli
Mary
M
Vaughan
Ellen
E
Karasik
Barbara
B
Foster
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins