Expression of a TGF-beta 1 inducible gene, TSC-36, causes growth inhibition in human lung cancer cell lines

TSC-36 (TGF-beta1-stimulated clone 36) is a TGF-beta1 inducible gene whose product is an extracellular glycoprotein that contains a single follistatin module. TSC-36 is highly expressed in the lung, but its physiological func tion is unknown. In an attempt to elucidate it, we investigated the effect of TSC-36 on proliferation of human lung cancer cell lines. We found a corr elation between expression of TSC-36 and cell growth: TSC-36 mRNA was not d etected in cells derived from small cell lung cancer (SCLC) cells, a highly aggressive neoplasm, but was detected in some non-small cell lung cancer ( NSCLC) cells, a moderately aggressive neoplasm. This suggested an antiproli ferative function for TSC-36. To address this question, NSCLC PC-14 cells, which express very low level of TSC-36 protein, were transfected with TSC-3 6 cDNA and the proliferative capacity of stable transfectants was determine d by measuring the doubling time, colony forming activity in soft agar and the level of incorporation of H-3-thymidine into DNA. Under normal culture conditions, the transfected cells showed a longer doubling time, lower plat ing efficiency and lower rate of DNA synthesis than the parental cells and the control neo transfectant cells. These findings suggested that expressio n of TSC-36 caused growth inhibition in human lung cancer cells. (C) 2000 E lsevier Science Ireland Ltd. All rights reserved.