Expression of the wild-type insulin-like growth factor II receptor gene suppresses growth and causes death in colorectal carcinoma cells

The insulin-like growth factor II receptor (IGFIIR) has been implicated as a tumor suppressor gene in human malignancy. Frequent mutation, loss of het erozygosity, and microsatellite instability (MSI) directly affecting the IG FIIR gene have been reported in several primary human tumor types. However, to our knowledge, dynamic functional evidence of a growth-suppressive role for IGFIIR has not yet been provided. We identified one MSI-positive color ectal carcinoma cell line, SW48, with monoallelic mutation in IGFIIR identi cal to that seen in primary colorectal carcinomas. A zinc-inducible constru ct containing the wild-type IGFIIR cDNA was stably transfected into SW48 ce lls. Growth rate and apoptosis mere compared between zinc-treated, untreate d, and untransfected cells. A twofold increase in IGFIIR protein expression was detected after zinc treatment in discrete clonal isolates of transfect ed SW48 cells. Moreover, zinc induction of exogenous wild-type IGFIIR expre ssion reproducibly decreased growth rate and increased apoptosis. These dat a prove that wild-type IGFIIR functions as a growth suppressor gene in colo rectal cancer cells and provide dynamic in vitro functional support for the hypothesis that IGFIIR is a human growth suppressor gene.