title: Downregulation and growth inhibitory role of FHL1 in lung cancer.
abstract: Four and a half Lin-11, Isl-1, Mac-3 (LIM) protein 1 (FHL1) has been linked to carcinogenesis. However, the role of FHL1 in lung cancer remains unclear and the detailed mechanism underlying its tumor suppressive role is poorly understood. The purpose of this study was to examine FHL1 expression in lung cancer patients and to investigate how it was associated with lung cancer cell growth. Immunoblotting and immunohistochemistry showed that FHL1 protein was downregulated in over 90% of 80 lung cancer patients. FHL1 expression was strongly correlated with tumor histological types (p < 10(-4) ) and the differentiation of the tumor (p = 0.002). FHL1 inhibited anchorage-dependent and -independent growth of human lung cancer cell lines. The inhibitory effects of FHL1 on lung cancer cell growth were associated with both the G1 and the G2/M cell cycle arrest concomitant with a marked inhibition of cyclin A, cyclin B1 and cyclin D as well as the induction of the cyclin dependent kinase inhibitors p21 (WAF1/CIP1) and p27 (Kip1). Direct intratumoral injection of an adenovirus expressing FHL1 dramatically suppressed the growth of A549 lung cancer cells in nude mice. Our data suggest that reduced expression of FHL1 may play an important role in the development and progression of lung cancer and that FHL1 may be a useful target for lung cancer gene therapy.
authors.affiliation: Department of Molecular Oncology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Niu
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Liang
authors.forename: Juntang
authors.initials: J
authors.lastname: Guo
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Qin
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lihua
authors.initials: L
authors.lastname: Ding
authors.forename: Bin
authors.initials: B
authors.lastname: Yuan
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xu
authors.forename: Jiezhi
authors.initials: J
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Qinong
authors.initials: Q
authors.lastname: Ye
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000502:physiology*; D060588:LIM Domain Proteins / Q000032:analysis / Q000502:physiology*; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D025521:Tumor Suppressor Proteins