The researchers investigated the effect of the loss of the Lkb1 tumor suppressor gene on gastrointestinal polyposis.
Germline mutations in LKB1 (also known as STK11) are associated with Peutz-Jeghers syndrome (PJS), a disorder with predisposition to gastrointestinal polyposis and cancer.
PJS polyps are unusual neoplasms characterized by marked epithelial and stromal overgrowth, but have limited malignant potential.
In a letter to the journal, the authors describe how Lkb1+/- mice develop intestinal polyps identical to those seen in individuals affected with PJS.
Despite compromised mortality, Lkb1+/- mouse embryonic fibroblasts showed resistance to transformation by activated Ha-Ras.
| Loss of Lkb1 gene renders cells resistant to transformation.
| Nature |
The phenotype is in agreement with the scarcity of Ras mutations seen in PJS polyps.
This suggests that loss of Lkb1 function as an early neoplastic event renders cells resistant to subsequent oncogene-induced transformation.
In addition, the Lkb1 transcriptome showed modulation of factors linked to angiogenesis, extracellular matrix remodeling, cell adhesion, and inhibition of Ras transformation.
Nabeel Bardeesy, of Harvard Medical School, Boston, concluded on behalf of the group, "Together, our data rationalize several features of PJS polyposis - notably its peculiar histopathological presentation and limited malignant potential.
"It also places Lkb1 in a distinct class of tumor suppressors."