Journal
CANCER RESEARCH
Volume 67, Issue 12, Pages 5622-5627Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-07-0762
Keywords
-
Categories
Ask authors/readers for more resources
Mutations in the serine-threonine tumor-suppressor kinase LKB1 are responsible for Peutz-jeghers syndrome, characterized by hamartomatous proliferation and an increased risk of developing cancer. Mutations in 101 have also been identified in sporadic cancers, suggesting a wider role for LKR1 in cancer that is not limited to hamartomatous polyposis syndromes. Here, We show that LKB1 catalytically deficient mutants, when introduced into DLD1p21(-/-)p53(-/-) colorectal cancer cells, allowed for progression of cells through to S phase of cell cycle and elicited the expression of Rb, cyclin E, and cyclin A2 whereas the introduction of LKB1 lead to G, cell cycle arrest independent of p21(WAF/CIP1) and/or p53 expression. Furthermore, we show that LKB1 catalytically deficient mutants activate the expression of cyclin D1 through recruitment to response elements within the promoter of the oncogene. In addition to compromising the tumor-suppressor function of LKB1, our findings highlight an emerging role for LKB1 catalytically deficient mutants, a gain of oncogenic properties.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available