Submitted on January 5, 2009
Revised on February 12, 2009
Accepted on February 16, 2009
Schlafen-3, A Novel Gene, Regulates Colonic Mucosal Growth during Aging
Bhaumik B Patel1, Yingjie Yu, Jianhua Du2, Arun K Rishi, Fazlul H. Sarkar2, Adi L Tarca2, Anil Wali2, and Adhip P.N. Majumdar1*
1 VAMC/ Wayne State University
2 Wayne State University
* To whom correspondence should be addressed. E-mail: a.majumdar{at}wayne.edu.
Although aging is associated with increased proliferation and decreased apoptosis in the colonic mucosa of Fischer 344 rats, the regulatory mechanisms are poorly understood. Gene expression profiling (Illumine platform) was carried out in freshly isolated colonic mucosal cells from young (4-6 months old) and aged (22-24 months old) Fischer-344 rats. Sixty six genes were differentially expressed in the colonic mucosa between young and old animals (p<0.05). In particular, the expression of Schlafen-3, a negative regulator of proliferation was decreased by 8-10-fold in the colonic mucosa of aged rats. Administration of wortmannin, which inhibited colonic mucosal proliferation in the colonic mucosa of aged rats stimulated the expression of Schlafen-3, indicating a growth regulatory role of this gene. To further determine the growth regulatory properties of Schlafen-3 gene, Schlafen-3 cDNA was transfected in colon cancer HCT-116 cells. This resulted in a 30-40% inhibition of cellular growth, accompanied by decreased expression of proliferating cell nuclear antigen (PCNA), Cyclin-D1 and reduced phosphorylation of Rb protein. In conclusion, our current study demonstrates that several genes involved in proliferation and apoptosis are differentially expressed in the colonic mucosa of young and aged rats. Schlafen-3, a novel negative regulator of growth, which is markedly downregulated in the colonic mucosa of the aged, may play a role in regulating colonic mucosal growth during aging.
