[Control of liver proliferation: structural, functional and molecular aspects].
After a period of active growth during embryonic and postnatal development, the liver attains a steady-state. In the adult organ, cell proliferation occurs after cell loss only or upon increased functional demand. It is triggered by an altered balance between growth inhibitory and stimulatory factors. The cell cycle of hepatocytes is controlled at various restriction points from G(0) to mitosis by cyclins which regulate cyclin-dependent kinases (cdk). Kinases or cyclin-cdk complexes are antagonized by a variety of inhibitory proteins. Actual commitment for proliferation is dependent on microenvironment, intralobular distribution as well as age and specific differentiation status and function, all of which play an important in modifying the actual mode of hepatocellular cell cycle transit. Major resection of liver parenchyma evokes a partially synchronized wave of systemic cell proliferation in a typical intralobular pattern. The size of the proliferative fraction appears limited by a priority to serve for the required specific function. It is altered by toxic or inflammatory processes or by changes of function. Multicellular organ-specific growth regulation and response is in contrast to monocellular escape from growth control in the clonal development of neoplasia. Genetic alterations during hepatocarcinogenesis, among many others constitutive expression of c-myc, mutations of p53, or amplification of cyclins, provide insight in the control of liver cell proliferation and their aberrant function in malignancy.
Rabes
H M
HM
Pathologisches Institut der Universität München.
D000375:Aging; D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005314:Embryonic and Fetal Development; D006498:Hepatectomy; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D008113:Liver Neoplasms / Q000473:pathology* / Q000503:physiopathology; D008115:Liver Regeneration; D008954:Models, Biological; D051381:Rats
D016213:Cyclins; D018844:Cyclin-Dependent Kinases