AWARDEE OF MEDICAL SCIENCES PRIZE

GU JIANREN

Abstract

Gu Jianren was born in Suzhou, Jiangsu, on Jan. 13, 1932. He graduated from the First Shanghai Medical College in 1954. As a molecular oncologist, he is director of National Laboratory For Oncogenes and Related Genes, Shanghai Cancer Institute, professor of molecular oncology in Shanghai Medical University, the member of National Biotechnology Program Board, the executive scientist of National Key Program For Human Gene Therapy. In 1994, he has elected to be the member academician of Chinese Academy of Engineering. Since 1995, he has been member of Award Assembly of General Motros Cancer Research Foundation.
He is the pioneer of molecular oncology and gene therapy research in China. In early 1960s, he demonstrated that the malignant phenotype of mouse hepatoma cells can be reversed towards that of normal hepatocytes in glycolytic metabolic pathways accompanied with inhibition of cancer cell growth by RNA extracted from normal animal liver. Since 1980s, his laboratory has devoted to the exploration of activated oncogenes and inactivated cancer suppressor genes involved in the development of human hepatocellular carcinoma (HCC). A number of protooncogenes or growth factor and receptor genes, such as N-ras, c-myc, c-ets 2, IGF Ⅱ and its receptor IGF Ⅰ R and IGF Ⅱ R, CSF Ⅰ and CSF Ⅰ R as well as EGF R were activated in HCC. Among the above genes, IGF Ⅱ, CSF-Ⅰ and TGFα and their receptor genes were demonstrated as multiple autocrine.paracrine systems involved in the hepatocarcinogenesis as well as progression of HCC. Therefore, in early 1980s he addressed the concept that each type of human cancer should have a spectrum of activated protooncogenes and inactivated cancer suppressor genes involved in the different stages of carcinogenesis and progression of malignant disease.
In the late 1980s, his laboratory initiated the genome study related to human HCC. He firstly proved that p53 mutation rate among the HCC samples derived from different geographical areas had remarkable difference, therefore, indicating that p53 mutation may be not a unique event in majority cases (>85%) of HCC development. On the contrary, the loss of heterozygosity (LOH) of chromosome 17p13.3 was demonstrated in more than 50% HCC cases without any geographical differences. Since 1992, his laboratory has focused on the positional cloning of the 17p13.3 region. Large scale sequencing of a hot spot within this area will be collaborated with GeneCore Inc. The isolation of cDNA clones and characterization of their structure and function in his laboratory is in progress. The other aspect of the genomic research has been performed using EST techniques by screening the differentially expressed cDNA clones derived from heart, liver, HCC cDNA libraries as well as subtractive cDNA libraries from liver minus HCC or HCC minus liver. So far, at least 4 full-length cDNA clones with potential valuem either as novel sequences or know genes with novel function have been identified.
His contribution in human gene therapy is to develop the first cancer clinical trial of brain tumor (HSV-TK) in China. He constructed a novel gene delivery system targeting to cancer cells that was patented in 1996.