Kh. Shin et al., GROWTH SUPPRESSION MEDIATED BY TRANSFECTION OF WILD-TYPE HMLH1 IN HUMAN CANCER-CELLS EXPRESSING ENDOGENOUS TRUNCATED HMLH1 PROTEIN, International journal of oncology, 12(3), 1998, pp. 609-615
Many genes that are frequently mutated in human cancer are known to be
involved in the control of normal cellular proliferation. One of the
genes involved in DNA mismatch repair is hMLH1, defective mutations of
which are found in some familial and various sporadic cancers. Althou
gh the DNA mismatch repair activity of hMLH1 has been identified, othe
r biological functions of hMLH1 have not been well investigated. To in
vestigate the effect of wild-type hMLH1 in cellular proliferation, wil
d-type hMLH1 cDNA was introduced into human colorectal carcinoma cell
line HCT116 and human gastric carcinoma cell line SNU-1, each containi
ng a homozygous non-sense mutation at codon 252 and 226 in hMLH1, repe
ctively. The hMLH1-transfected stable clones showed mRNA and protein e
xpression of transfected hMLH1. Three in vitro cell growth experiments
demonstrated that compared with parental and vector-transfected contr
ol counterparts, both hMLH1-transfected HCTI16 and SNU-1 clones displa
yed: i) decreased cellular proliferation; ii) a significant decrease i
n the rate of DNA synthesis and iii) a dramatic reduction of anchorage
-independence and the size of colonies in semisolid medium. In additio
n to DNA repair activity, these results suggest that hMLH1 may play a
role in the negative regulation of HCT116 and SNU-1 cell growth.