Regulation of cell proliferation, apoptosis, and carcinogenesis by activin.
The aim of this review is to provide insight into the molecular mechanisms by which activin A modulates cell proliferation, apoptosis, and carcinogenesis in vitro and in vivo. Activin A, a member of the TGFbeta superfamily, has various effects on diverse biological systems, including cell growth inhibition in many cell types. However, the mechanism(s) by which activin exerts its inhibitory effects are not yet understood. This review highlights activin's effects on activin receptors and signaling pathway, modulation of activin signaling, and regulation of cell proliferation and apoptosis by activin. Based on the experiences of all the authors, we emphasized cell cycle inhibitors such as p16 and p21 and regulators of apoptosis such as p53 and members of the bcl-2 family. Aside from activin's inhibition of cell proliferation and enhancement of apoptosis, other newly developed methods for molecular studies of apoptosis by activin were briefly presented that support the role of activin as an inhibitor of carcinogenesis and cancer progression. These methods include subtractive hybridization based on covalent bonding, a simple and accurate means to determine molecular profile of as few as 20 cells based on an RNA-PCR approach, and a messenger RNA-antisense DNA interference phenomenon (D-RNAi), resulting in a long-term gene knockout effects.
Chen
Ye-Guang
YG
Division of Biomedical Sciences, University of California, Riverside, California 92521, USA.
Lui
Hannah M
HM
Lin
Shi-Lung
SL
Lee
Jeffery M
JM
Ying
Shao-Yao
SY
D029404:Activin Receptors / Q000502:physiology; D028341:Activins / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology; D006801:Humans; D028322:Inhibin-beta Subunits / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits; D029404:Activin Receptors