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Transforming growth factor beta 1 partially suppresses the transformed phenotype of ras-transformed hepatocytes
R Serra1, M F Verderame, H C Isom
1Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey 17033.
Abstract:
The effect of transforming growth factor beta type 1 (TGF-beta 1) on DNA synthesis, anchorage-dependent and anchorage-independent proliferation, cytoskeletal organization, and gene expression in ras-transformed simian virus 40 (SV40)-immortalized hepatocyte cell lines was measured. An SV40-immortalized cell line (CWSV1), a control neo-transfected and selected cell line (N1), and neo+ras-transfected and selected cell lines (NR3 and NR4) were used for this study. CWSV1 and N1 cells do not grow in soft agarose and are not tumorigenic. The ras-transformed hepatocytes NR3 and NR4 grow in soft agar and are tumorigenic. TGF-beta 1 treatment did not inhibit DNA synthesis or anchorage-dependent growth in the SV40-immortalized hepatocyte cell line CWSV1 or in the ras-transformed hepatocytes. TGF-beta 1 treatment inhibited anchorage-independent growth, increased actin cytoskeleton organization, and altered the morphology of ras-transformed hepatocytes; that is, with regard to all three of these properties, TGF-beta 1-treated ras-transformed hepatocytes more closely resembled the immortalized parent cell line. c-Ha-ras and c-myc RNA levels were not altered in TGF-beta 1-treated NR4 cells. TGF-beta 1 treatment did alter expression of some genes in NR4 cells. The level of expression of alpha 1 integrin RNA was higher in CWSV1 cells than in NR4 cells and increased in NR4 cells when they were treated with TGF-beta 1. Similarly, the levels and profiles of integrins on the cell surface of CWSV1 cells compared to NR4 cells, as determined by cell surface protein iodination, differed and in TGF-beta 1-treated NR4 cells more closely resembled the surface integrin profile for CWSV1 cells.
Insights
Transforming growth factor beta 1 (TGF-beta 1) reversed some oncogenic properties of ras-transformed hepatocytes. TGF-beta 1 treatment restored normal anchorage-independent growth, cytoskeletal organization, and integrin expression in cancer cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- Hepatocyte cell lines are crucial models for studying liver cancer.
- Ras-transformed cells exhibit oncogenic properties like tumorigenicity and anchorage-independent growth.
- Transforming growth factor beta 1 (TGF-beta 1) is a key regulator of cell behavior.
Purpose of the Study:
- To investigate the effects of TGF-beta 1 on ras-transformed hepatocytes.
- To compare TGF-beta 1's impact on normal immortalized hepatocytes versus cancer cells.
- To analyze changes in proliferation, cytoskeleton, and gene expression.
Main Methods:
- Utilized simian virus 40 (SV40)-immortalized hepatocyte cell lines (CWSV1, N1) and ras-transfected variants (NR3, NR4).
- Assessed DNA synthesis, anchorage-dependent and -independent proliferation, and cytoskeletal organization.
- Measured gene expression of c-Ha-ras, c-myc, and alpha 1 integrin RNA, alongside cell surface integrin profiles.
Main Results:
- TGF-beta 1 did not inhibit DNA synthesis or anchorage-dependent growth in any cell line.
- TGF-beta 1 inhibited anchorage-independent growth and enhanced actin cytoskeleton organization in ras-transformed cells.
- TGF-beta 1 treatment altered morphology and integrin expression in ras-transformed cells, making them resemble the parent cell line.
Conclusions:
- TGF-beta 1 can reverse specific oncogenic phenotypes in ras-transformed hepatocytes.
- The study highlights TGF-beta 1's role in modulating cell growth, cytoskeleton, and integrin expression.
- TGF-beta 1 treatment offers a potential strategy to restore normal cellular characteristics in liver cancer models.