Association between expression of transforming growth factor-alpha and progression of hepatocellular foci to neoplasms.
Hepatocarcinogenesis was initiated in rats with a single dose of either of two chemical mutagens--benzo[a]pyrene diolepoxide I and methyl(acetoxymethyl)nitrosamine--administered 15 h after partial hepatectomy. The development of hepatocellular foci and neoplasms was then promoted with dietary phenobarbital given for 45 or 62 weeks. Formalin-fixed tissue specimens that contained hepatic neoplasms and altered hepatocellular foci were screened for expression of the oncodevelopmental marker glutathione-S-transferase (placental form) (GSTP) and transforming growth factor-alpha (TGF-alpha) using immunohistochemistry. All (100%) hepatocellular carcinomas expressed both GSTP and TGF-alpha, as did most hepatocellular adenomas (greater than 80%). However, quantitative stereologic analysis of treated and control livers revealed that GSTP-positive foci were 10-30 times more frequent than TGF-alpha-positive foci. Foci with homogeneous expression of GSTP generally displayed heterogeneous expression of TGF-alpha with reaction product most prominent at their peripheries. Less frequently homogeneous TGF-alpha-positive foci were seen within GSTP-positive foci. The average volumes of those GSTP-positive foci that also expressed TGF-alpha were significantly greater than those of the entire sets of GSTP-positive foci. These results suggest that expression of TGF-alpha may distinguish a subset of GSTP-positive foci that have a growth advantage and increased probability of progression to neoplasia.
Kaufmann
W K
WK
Department of Pathology, University of North Carolina, Chapel Hill 27599-7295.
Zhang
Y
Y
Kaufman
D G
DG
D000236:Adenoma / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens; D002277:Carcinoma / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002911:Chrysenes; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives; D005982:Glutathione Transferase / Q000096:biosynthesis; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis*
D002273:Carcinogens; D002911:Chrysenes; D016211:Transforming Growth Factor alpha; C014659:methyl(acetoxymethyl)nitrosamine; C037783:1,2-dihydroxy-epoxy-1,2,3,4-tetrahydro-5-methylchrysene; D005982:Glutathione Transferase; D004128:Dimethylnitrosamine