DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity.
The human DLC-1 (deleted in liver cancer 1) gene was cloned from a primary human hepatocellular carcinoma (HCC) and mapped to the chromosome 8p21-22 region frequently deleted in common human cancers and suspected to harbor tumor suppressor genes. DLC-1 was found to be deleted or downregulated in a significant number of HCCs. We expanded our investigations to other cancers with recurrent deletions of 8p22, and in this study examined alterations of DLC-1 in primary human breast tumors, human breast, colon, and prostate tumor cell lines. Genomic deletion of DLC-1 was observed in 40% of primary breast tumors, whereas reduced or undetectable levels of DLC-1 mRNA were seen in 70% of breast, 70% of colon, and 50% of prostate tumor cell lines To see whether DLC-1 expression affects cell growth and tumorigenicity, two breast carcinoma cell lines lacking the expression of endogenous gene were transfected with the DLC-1 cDNA. In both cell lines, DLC-1 transfection caused significant growth inhibition and reduction of colony formation. Furthermore, introduction of the DLC-1 cDNA abolished the in vivo tumorigenicity in nude mice, suggesting that the DLC-1 gene plays a role in breast cancer by acting as a bona fide tumor suppressor gene.
Yuan
Bao-Zhu
BZ
Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Zhou
Xiaoling
X
Durkin
Marian E
ME
Zimonjic
Drazen B
DB
Gumundsdottir
Katrin
K
Eyfjord
Jorunn E
JE
Thorgeirsson
Snorri S
SS
Popescu
Nicholas C
NC
D000230:Adenocarcinoma / Q000235:genetics; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D015197:Carcinogenicity Tests / Q000379:methods; D002455:Cell Division / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D020690:GTPase-Activating Proteins; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology; D012016:Reference Values; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D025521:Tumor Suppressor Proteins