Deletions and/or loss of heterozygosity (LOH) on chromosome 15 (15q15 and 15q21) have been found in several human
tumors, including
carcinomas of the colorectum, breast, lung, prostate, and bladder, suggesting the presence of potential tumor suppressor gene(s) in this particular region of chromosome 15. GCIP also called CCNDBP1, DIP1, or HHM, localized at chromosome 15q15, is a recently identified helix-loop-helix leucine zipper (HLH-ZIP)
protein without a basic region like the Id family of
proteins. In this study, we reported that the expression of GCIP was significantly downregulated in several different human
tumors, including
breast tumor, prostate
tumor, and colon
tumors. In human colon
tumors, both
mRNA and
protein expression levels of GCIP were decreased significantly compared to the normal tissues. Treatment of
colon cancer cells SW480 with
sodium butyrate (NaB), which induces
colon cancer cell differentiation, can induce the upregulation of GCIP expression, suggesting that the
protein functions as a negative regulator in cell proliferation. Overexpression of GCIP in SW480
colon cancer cell line resulted in a significant inhibition on
tumor cell colony formation, while silencing of GCIP expression by
siRNA can promote cell colony formation. Furthermore, overexpression of GCIP inhibited the transcriptional activity of
cyclin D1 promoter and the expression of
cyclin D1 protein in the cell. Finally, we demonstrate that GCIP specifically interacts with one of the class III
HDAC proteins, SirT6, which is important for maintaining
genome stability. Together, our data suggest a possible function of GCIP in
tumor suppression.