Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here to sign up for SAGE Journal Email Alerts today!

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Do Youn Park
Right arrow Articles by Kang Suek Suh
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Do Youn Park,
Right arrow Articles by Kang Suek Suh,
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Expression of Transforming Growth Factor (TGF)-β1 and TGF-β Type II Receptor in Preneoplastic Lesions During Chemical Hepatocarcinogenesis of Rats

Do Youn Park

Department of Pathology, Pusan National University College of Medicine, Pusan, Korea

Soon Yeol Hwang

Department of Pathology, Pusan National University College of Medicine, Pusan, Korea

Kang Suek Suh

Department of Pathology, Pusan National University College of Medicine, Pusan, Korea, pdy220{at}netsgo.com

Transforming growth factor (TGF)-β1 is an important apoptotic growth inhibitor of hepatocyte proliferation, and the expression of TGF-β1, which regulates cell proliferation, is closely associated with the expression level of TGF- β type II receptor (TGR2). Moreover, TGF-β1 expression has been regarded to be an important change in hepatocarcinogenesis . We undertook this study to investigate the gene expression and protein localization of TGF-β1 and TGR2 and their relationship with apoptosis in the chemically induced hepatocarcinogenesi s of the rat, as produced using Solt and Farber's method, during the promotion stage (up to 56 days after partial hepatectomy). Northern blot analysis showed a slight, but not a significant, increase in TGF-β1 transcripts, and a significant decrease in the TGR2 transcripts during the later stage of our experiments (42 days after partial hepatectomy). Immunohistochemical study showed that TGF-β 1-positive preneoplastic hepatocytes increased with time, and this correlated with an increase of TGR2 negative or reduced TGR2 expressed preneoplastic lesions. The TUNEL method revealed that apoptotic cells increased with time and were more numerous in the adjacent liver parenchyme than preneoplastic lesions. Our data suggest that the expressions of TGF-β1 and TGR2 are significantly altered during the promotion stage of hepatocarcinogenesi s of rat and that these changes might contribute to the development and progression of preneoplastic lesions.

Key Words: TGF-β1 • TGF-β type II receptor • preneoplastic lesions • northern blot • immunohistochemistry • apoptosis • chemical hepatocarcinogenesis • rat.

References

  • Abou-Shady M., Baer HU, Friess H., Berberat P., Zimmermann A., Graber H., Gold LI, Korc M., Buchler MW (1999). Transforming growth factor-betas and their signaling receptors in human hepatocellular carcinoma. Am J Surg 177: 209—215.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bissel DM, Wang SS, Jarnagin WR, Roll FJ ( 1995). Cell-specific expression of transforming growth factor-β in rat liver. J Clin Invest 96: 447—455.[Web of Science][Medline] [Order article via Infotrieve]
  • Bursch W., Lauer B., Timmermann-Trosiener I., Barthel G., Schuppler J., Schulte-Hermann R. (1984). Controlled death (apoptosis) of normal and putative preneoplastic cells in rat liver following withdrawal of tumor promoters. Carcinogenesis 5: 453—458.[Abstract/Free Full Text]
  • Cui W., Fowlis DJ, Bryson S., Duffie E., Ireland H., Balman A., Akhurst RJ (1996). TGF-β1 inhibits the formation of benign skin tumors but enhance progression to invasive spindle carcinomas in transgenic mice. Cell 86: 531—542.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • De Miglio MR, Simile MM, Muroni MR, Pusceddu DR, Calvisi D., Carru A., Seddaiu MA, Daino L., Deiana L., Pascale RM, Feo F. (1999). Correlation of c-myc overexpression and amplification with progression of preneoplastic liver lesions to malignancy in the poorly susceptible wistar rat strain. Mol Carcinog 25: 21—29.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Eastham JA, Truong LD, Rogers E., Kattan M., Flanders KC, Scardino PT, Thompson TC (1995). Transforming growth factor β1; comparative immunohistochemical localization in human primary and metastatic prostate cancer. Lab Invest 73: 628—635.[Web of Science][Medline] [Order article via Infotrieve]
  • Evarts RP, Nakatsukasa H., Marsden ER, Hsia CC, Dunsford HA, Thorgeirsson SS (1990). Cellular and molecular changes in the early stages of chemical hepatocarcinogenesi s in the rat. Cancer Res 50: 3439— 3444.[Abstract/Free Full Text]
  • Farber E., Sarma DS (1987). Hepatocarcinogenesis: A dynamic cellular perspective. Lab Invest 56: 4—22.[Web of Science][Medline] [Order article via Infotrieve]
  • Fukuda K., Kojiro M., Chiu JF ( 1993). Induction of apoptosis by TGF-beta 1 in the rat hepatoma cell line MCA-RH7777; a possible association with tissue transglutaminase expression. Hepatology 18: 945—953.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Fynn TM, Reiss M. (1993). Resistance to inhibition of cell growth by transforming growth factor β and its role in oncogenesis. Crit Rev Onco 4: 493—540.
  • Gressner AM, Polzar B., Lahme B., Mannherz HG (1996). Induction of rat liver parenchymal cell apoptosis by hepatic myofibroblasts via transforming growth factor beta. Hepatology 23: 571—581.[Web of Science][Medline] [Order article via Infotrieve]
  • Inagaki M., Moustakas A., Lin HY, Lodish HF, Carr BI ( 1993). Growth inhibition by transforming growth factor type I is restored in TGF-beta resistant hepatoma cells after expression of TGF-beta receptor type II cDNA. Proc Natl Acad Sci USA 90: 5359—5363.[Abstract/Free Full Text]
  • International Working Party ( 1996). Terminology of nodular hepatocellular lesions. Hepatology 22: 983—993.
  • Ito N., Kawata S., Tamura S. (1991). Elevated levels of transforming growth factor-beta messenger RNA and its polypeptide in human hepatocellular carcinoma. Cancer Res 51: 4080—1083.[Abstract/Free Full Text]
  • Kehrl JH (1991). Transforming growth factor-beta; an important mediator of immunoregulation. Int J Cell Cloning 9: 438—450.[Medline] [Order article via Infotrieve]
  • Lim JK, Park SC, Song KY, Park TJ, Lee MS, Kim SJ, Hyun BH ( 1999). Regulation of selection of liver nodules initiated with N-nitrosodiethylamine and promoted with nodularin injections in Fischer 344 male rats by reciprocal expression of transforming growth factor-β1 and its receptors. Mol Carcinog 26: 83—92.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Lin JK, Chou CK ( 1992). In vitro apoptosis in the human hepatoma cell line induced by transforming growth factor-beta 1. Cancer Res 52: 385— 388.[Abstract/Free Full Text]
  • Massague J., Like B. ( 1985). Cellular receptors for type beta transforming growth factor: ligand binding and affinity labeling in human and rodent cell lines. JBiol Chem 260: 2636—2645.[Abstract/Free Full Text]
  • Murakami H., Sanderson ND, Nagy P., Marino PA, Merlino GP, Thorgeirsson SS (1993). Transgenic mouse model for synergistic effects of nuclear oncogenes and growth factors in tumorigenesis: Interaction of c-myc and transforming growth factor-alpha in hepatic oncogenesis. Cancer Res 53: 1719— 1723.[Abstract/Free Full Text]
  • Nakatsukasa H., Evarts RP, Hsia CC, Marsden ER, Thorgeirsson SS (1991). Expression of transforming growth factor-β1 during chemical hepatocarcinogenesis in the rat. Lab Invest 65: 511—517.[Web of Science][Medline] [Order article via Infotrieve]
  • Oft M., Peli J., Rudaz C., Schwarz H., Beug H., Reichmann E. (1996). TGF-β1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev 10: 2462—2477.[Abstract/Free Full Text]
  • Pascale RM, De Miglio MR, Muroni MR, Simile MM, Daino L., Seddaiu MA, Nufris A., Gaspa L., Deiana L., Feo F. (1996). C-myc amplification in premalignant and malignant lesions induced in rat liver by the resistant hepatocyte model. Int J Cancer 68: 136—142.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Pierce DF, Gorska AE, Chytil A., Meise KS, Page DL, Coffrey RJ Jr, Moses HL (1995). Mammary tumor suppression by transforming growth factor β1 transgenic expression. Proc Natl Acad Sci USA 92: 4254—4258.[Abstract/Free Full Text]
  • Reeder MK, Isom HC ( 1996). Effect of transforming growth factor beta on rat hepatocyte cell lines depends upon the state of tumorigenic progression. Cell Growth Diff 7: 449—460.[Abstract]
  • Reisenbichler H., Chari RS, Boyer IJ, Jirtle RL (1994). Transforming growth factor-β receptors type I, II and III in phenobarbital-promoted rat liver tumors. Carcinogenesis 15: 2763—2767.[Abstract/Free Full Text]
  • Santoni-Rugiu E., Jensen MR, Factor VM, Thorgeirsson SS (1999). Acceleration of c-myc-induced hepatocarcinogenesi s by co-expression of transforming growth factor-alpha in transgenic mice in associated with TGF-β1 signaling disruption. Am J Pathol 154: 1693—1700.[Abstract/Free Full Text]
  • Schulte-Hermann R., Bursch W., Low-Baseli A., Wager A., Grasl-Kraupp B. (1997). Apoptosi s in the liver and its role in hepatocarcinogenesis. Cell Biol Toxicol 13: 339—348.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Segarini PR (1993). TGF-β receptors: a complicated system of multiple binding proteins. Biochem Biophys Acta 1155: 269—275.[Medline] [Order article via Infotrieve]
  • Shirai Y., Kawata S., Tamura S., Ito N., Tsushima H., Takaishi K., Kiso S., Matsuzawa Y. (1994). Plasma transforming growth factor-betal in patients with hepatocellular carcinoma. Cancer 73: 2275—2279.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Solt DB, Medline A., Farber E. (1977). Rapid emergence of carcinogen-induced hyperplastic lesions in a new model for the sequential analysis of liver carcinogenesis. Am J Pathol 88: 595—618.[Web of Science][Medline] [Order article via Infotrieve]
  • Stenius U. (1993). Different inhibition of DNA synthesis by transforming growth factor β and phenobarbital on GST-P-positive and GST-P-negative hepatocytes. Carcinogenesis 14: 159—161.[Abstract/Free Full Text]
  • Stinchcombe S., Buchmann A., Bock KW, Schwarz M. (1995). Inhibition of apoptosis during 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediate d tumour promotion in rat liver. Carcinogenesis 16: 1271—1275.[Abstract/Free Full Text]
  • Taknami I., Imamuma T., Hashizume T., Kikuchi K., Yamamoto Y., Kodaira S. (1996). Expression of PDGF, IGF-II, bFGF and TGF-β1 in pulmonary adenocarcinoma. Pathol Res Pract 192: 1113—1120.[Web of Science][Medline] [Order article via Infotrieve]
  • Tatematsu M., Mera Y., Inoue T., Satoh K., Sato K., Ito N. (1988). Stable phenotypic expression of glutathione S-transferase placental type and unstable phenotypic expression of gamma-glutamyltransferas e in rat liver preneoplastic and neoplastic lesions. Carcinogenesis 9: 215—220.[Abstract/Free Full Text]
  • Tsuchida K., Lewis KA, Mathews LS, Vale WW (1993). Molecular characterization of rat transforming growth factor-β type II receptor. Biochem Biophys Res Commun 191: 790—795.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Wollenberg GK, Semple E., Quinn BA, Hayes MA (1987). Inhibition of proliferation of normal, preneoplastic, and neoplastic rat hepatocytes by transforming growth factor-beta. Cancer Res 47: 6595—6600.[Abstract/Free Full Text]
  • Wrana JL, Attisano L., Wieser R., Ventura F., Massague J. (1994). Mechanism of activation of the TGF-β receptor. Nature 370: 341—347.[CrossRef][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 29, No. 5, 541-549 (2001)
DOI: 10.1080/019262301317226348
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Toxicol PatholHome page
A. L. Tozzi Spinardi-Barbisan, L. F. Barbisan, J. Lauro Viana De Camargo, and M. Aparecida Marchesan Rodrigues
Infiltrating CD8+ T Lymphocytes, Natural Killer Cells, and Expression of IL-10 and TGF-{beta}1 in Chemically Induced Neoplasms in Male Wistar Rats
Toxicol Pathol, August 1, 2004; 32(5): 548 - 557.
[Abstract] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Do Youn Park
Right arrow Articles by Kang Suek Suh
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Do Youn Park,
Right arrow Articles by Kang Suek Suh,
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?