Characterization Of The Two Differentiation-inducing CDNAs Isolated From Human Lung Cancer Cells By Retinoic Acid-Activation

It's known that the multistep carcinogenic process is often characterized by loss of normal control over proliferation and aberrant patterns of difFerentiation. The principle of tumor differentiation therapy has been developed on the basis of these facts. It doesn't attempt to kill tumor cells, but focuses on the suppression of cell proliferation and the induction of terminal differentiation. During the last decade, our lab has been developing a novel strategy for isolating differentiation-inducing genes from human cancers: terminal differentiation of human cancer cell lines is induced by all-trans-retinoic acid(RA), then repeated subtraction hybridization between cDNA libraries constructed from cells before and after RA-treatrnent is used' to isolate genes specifically activated by RA. The biological effects of these genes on parental cells are then tested in vitro. So far, a novel gene—RATS1 has been isolated from esophageal cancer cell line which possesses strong proliferation-suppressing and differentiation-inducing effect.With similar strategy, our lab also attempted to isolate those differentiation-inducing genes from lung cancer cells: three cDNA libraries were constructed, one was from human lung adenocarcinoma cell line GLC-82, named Lib.GLC-82; the other were from GLC-82 cells treated with RA for 1 and 4 days, named Lib.GLC-82.RAl and Lib.GLC-82.RA4. After the 6th round of subtraction hybridization, 124 differential cDNA clones were obtained. This study is concerned on identifying those novel genes, investigating their correlation with carcinogenesis of lung cancer, dissecting the mechanism of RA's action, and evaluate their biological functions in their parental cells GLC-82.