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- Publisher Website: 10.1097/00000658-199508000-00009
- Scopus: eid_2-s2.0-0029100622
- PMID: 7639583
- WOS: WOS:A1995RM73400009
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Article: Transforming growth factor-beta receptors and mannose 6- phosphate/insulin-like growth factor-II receptor expression in human hepatocellular carcinoma
Title | Transforming growth factor-beta receptors and mannose 6- phosphate/insulin-like growth factor-II receptor expression in human hepatocellular carcinoma |
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Authors | |
Issue Date | 1995 |
Citation | Annals of Surgery, 1995, v. 222, n. 2, p. 171-178 How to Cite? |
Abstract | Objective: The authors examined the expression of transforming growth factor-beta receptor (TGF-βr) types I and II and the mannose 6- phosphate/insulin like growth factor-II receptor (M6-P/IGF-IIr) in human hepatocellular carcinoma (HCC). Summary Background Data: Transforming growth factor beta (TGF-β) is part of a superfamily of peptide signaling molecules that play an important role in modulating cell growth. It is secreted as a latent complex and therefore, must be activated to elicit a biological response. Bioactivation of the TGF-β complex is facilitated by binding to the M6-P/IGF-IIr. Once activated, TGF-β exerts its effects by binding to specific cell membrane TGF-β receptors. The loss of responsiveness of hepatocytes to TGF-β has been implicated in hepatocarcinogenesis and could result from a loss in the expression of either the TGF-β receptors or the M6-P/IGF-IIr. Methods: Human hepatocellular carcinomas and surrounding normal tissue were collected from operating room samples and snap-frozen in liquid nitrogen (n = 13). Tissues from two tumors were fixed in Omni-fix for sectioning and immunohistochemistry staining for the M6-P/IGF-IIr and TGF- β1. RNA was extracted from both normal and malignant liver tissue and analyzed using an RNase protection assay. SDS-PAGE of purified membrane hybridized with 125I-TGF-β1 and 125I-IGF-II was used to determine the TGF-β type I (TGF-βrI) and type II (TGF-βrII) receptors and MG-P/IGF-IIr protein levels, respectively. Gels were quantitated by phosphorimager, and a paired t test was used for statistical analysis. Results: In HCC, a 60% (p < 0.01) and 49% (p < 0.02) reduction in the mRNA levels for TβrI and TβrII, respectively, relative to the receptor levels in surrounding normal liver, was shown. A similar decrease in the receptor protein levels also was observed. The M6-P/IGF-IIr mRNA and protein levels were reduced in 7 of 11 hepatocellular Carcinomas. Immunohistochemical staining demonstrated an absence of intracellular TGF-β1 and reduced M6-P/IGF-IIr in the hepatocellular carcinoma cells. Conclusions: These results demonstrate that human HCCs have a significantly reduced expression of both the TGF-βrI- and TGF-βrII-signaling receptors for TGF-β. This may provide a selective growth advantage to the HCC by allowing them to escape the mito-inhibitory effects of activated TGF-β. Furthermore, in the subset of HCC in which the expression of the M6-P/IGF-IIr is downregulated, the bioactivation of TGF-β also may be impaired. |
Persistent Identifier | http://hdl.handle.net/10722/266755 |
ISSN | 2023 Impact Factor: 7.5 2023 SCImago Journal Rankings: 2.729 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Sue, S. R. | - |
dc.contributor.author | Chari, R. S. | - |
dc.contributor.author | Kong, F. M. | - |
dc.contributor.author | Mills, J. J. | - |
dc.contributor.author | Fine, R. L. | - |
dc.contributor.author | Jirtle, R. L. | - |
dc.contributor.author | Meyers, W. C. | - |
dc.date.accessioned | 2019-01-31T07:19:29Z | - |
dc.date.available | 2019-01-31T07:19:29Z | - |
dc.date.issued | 1995 | - |
dc.identifier.citation | Annals of Surgery, 1995, v. 222, n. 2, p. 171-178 | - |
dc.identifier.issn | 0003-4932 | - |
dc.identifier.uri | http://hdl.handle.net/10722/266755 | - |
dc.description.abstract | Objective: The authors examined the expression of transforming growth factor-beta receptor (TGF-βr) types I and II and the mannose 6- phosphate/insulin like growth factor-II receptor (M6-P/IGF-IIr) in human hepatocellular carcinoma (HCC). Summary Background Data: Transforming growth factor beta (TGF-β) is part of a superfamily of peptide signaling molecules that play an important role in modulating cell growth. It is secreted as a latent complex and therefore, must be activated to elicit a biological response. Bioactivation of the TGF-β complex is facilitated by binding to the M6-P/IGF-IIr. Once activated, TGF-β exerts its effects by binding to specific cell membrane TGF-β receptors. The loss of responsiveness of hepatocytes to TGF-β has been implicated in hepatocarcinogenesis and could result from a loss in the expression of either the TGF-β receptors or the M6-P/IGF-IIr. Methods: Human hepatocellular carcinomas and surrounding normal tissue were collected from operating room samples and snap-frozen in liquid nitrogen (n = 13). Tissues from two tumors were fixed in Omni-fix for sectioning and immunohistochemistry staining for the M6-P/IGF-IIr and TGF- β1. RNA was extracted from both normal and malignant liver tissue and analyzed using an RNase protection assay. SDS-PAGE of purified membrane hybridized with 125I-TGF-β1 and 125I-IGF-II was used to determine the TGF-β type I (TGF-βrI) and type II (TGF-βrII) receptors and MG-P/IGF-IIr protein levels, respectively. Gels were quantitated by phosphorimager, and a paired t test was used for statistical analysis. Results: In HCC, a 60% (p < 0.01) and 49% (p < 0.02) reduction in the mRNA levels for TβrI and TβrII, respectively, relative to the receptor levels in surrounding normal liver, was shown. A similar decrease in the receptor protein levels also was observed. The M6-P/IGF-IIr mRNA and protein levels were reduced in 7 of 11 hepatocellular Carcinomas. Immunohistochemical staining demonstrated an absence of intracellular TGF-β1 and reduced M6-P/IGF-IIr in the hepatocellular carcinoma cells. Conclusions: These results demonstrate that human HCCs have a significantly reduced expression of both the TGF-βrI- and TGF-βrII-signaling receptors for TGF-β. This may provide a selective growth advantage to the HCC by allowing them to escape the mito-inhibitory effects of activated TGF-β. Furthermore, in the subset of HCC in which the expression of the M6-P/IGF-IIr is downregulated, the bioactivation of TGF-β also may be impaired. | - |
dc.language | eng | - |
dc.relation.ispartof | Annals of Surgery | - |
dc.title | Transforming growth factor-beta receptors and mannose 6- phosphate/insulin-like growth factor-II receptor expression in human hepatocellular carcinoma | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1097/00000658-199508000-00009 | - |
dc.identifier.pmid | 7639583 | - |
dc.identifier.scopus | eid_2-s2.0-0029100622 | - |
dc.identifier.volume | 222 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 171 | - |
dc.identifier.epage | 178 | - |
dc.identifier.isi | WOS:A1995RM73400009 | - |
dc.identifier.issnl | 0003-4932 | - |