PMID- 8597531
OWN - NLM
STAT- MEDLINE
DCOM- 19960424
LR  - 20220331
IS  - 0899-1987 (Print)
IS  - 0899-1987 (Linking)
VI  - 15
IP  - 3
DP  - 1996 Mar
TI  - Liver regeneration and hepatocarcinogenesis in transforming growth 
      factor-alpha-targeted mice.
PG  - 183-9
AB  - Transforming growth factor-alpha (TGF alpha), a member of the epidermal growth 
      factor receptor ligand family, has been implicated in the regeneration and 
      transformation of liver. Our recent development of mice that are homozygous for a 
      disrupted TGF alpha gene allowed us to assess the requirement for this growth 
      factor in these complex processes. We report here that although a 70% hepatectomy 
      produced a significant increase in hepatic TGF alpha protein levels in wild-type 
      mice, liver regeneration nevertheless proceeded normally in the absence of the 
      growth factor. The hepatocyte labeling indices determined for homozygous targeted 
      and wild-type mice at 36 and 48 h after hepatectomy were comparable, and the 
      total liver DNA to body weight ratios 8 d after hepatectomy were essentially 
      identical for the two genotypes. These results indicate that TGF alpha, is not 
      necessary for liver regeneration. To test its requirement in liver 
      carcinogenesis, young mice were administered single doses of diethylnitrosamine 
      (DEN) with or without subsequent chronic treatment with the promoting agent 
      phenobarbital (PB). Both wild-type and homozygous mutant male mice treated with 
      DEN or DEN plus PB developed multiple preneoplastic foci or tumors by 9 mo of age 
      with relatively high incidence. However, while five of 88 tumors in wild-type 
      mice attained a diameter greater than 5 mm and were classified as hepatocellular 
      carcinomas, none of 132 tumors in livers of targeted mice reached this size. 
      Furthermore, three of these large wild-type tumors expressed significantly 
      elevated levels of TGF alpha protein compared with normal liver. These results 
      indicate that TGF alpha is not required for early events in chemically induced 
      hepatocarcinogenesis but suggest that it could be important in the progression 
      from small preneoplastic foci to large tumors.
FAU - Russell, W E
AU  - Russell WE
AD  - Department of Pediatrics, Vanderbilt Cancer Center, Vanderbilt University, 
      Nashville, Tennessee, USA.
FAU - Kaufmann, W K
AU  - Kaufmann WK
FAU - Sitaric, S
AU  - Sitaric S
FAU - Luetteke, N C
AU  - Luetteke NC
FAU - Lee, D C
AU  - Lee DC
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (Carcinogens)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 3IQ78TTX1A (Diethylnitrosamine)
SB  - IM
MH  - Animals
MH  - Carcinogens/toxicity
MH  - *Cocarcinogenesis
MH  - Diethylnitrosamine/toxicity
MH  - Hepatectomy
MH  - Humans
MH  - Iodine Radioisotopes
MH  - Liver Neoplasms, Experimental/chemically induced/*etiology
MH  - Liver Regeneration/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Precancerous Conditions/chemically induced/etiology
MH  - Radioimmunoassay
MH  - Transforming Growth Factor alpha/*physiology
EDAT- 1996/03/01 00:00
MHDA- 1996/03/01 00:01
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 1996/03/01 00:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
AID - 10.1002/(SICI)1098-2744(199603)15:3<183::AID-MC4>3.0.CO;2-J [pii]
AID - 10.1002/(SICI)1098-2744(199603)15:3<183::AID-MC4>3.0.CO;2-J [doi]
PST - ppublish
SO  - Mol Carcinog. 1996 Mar;15(3):183-9. doi: 
      10.1002/(SICI)1098-2744(199603)15:3<183::AID-MC4>3.0.CO;2-J.