Alterations in guanine nucleotide regulatory protein expression and activity in human hepatocellular carcinoma

C. Schmidt, Iain H. Mckillop, Paul A. Cahill, James V. Sitzmann

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Alterations in the expression and activity of guanine nucleotide regulatory proteins (G proteins) have been linked to the growth of several human tumors. We hypothesized that the expression and activity of G proteins are altered in human hepatocellular carcinoma (HCC). The expression of Gi and Gs proteins was determined in six human tumors and six normal controls (adjacent nonneoplastic liver) by Western blotting using specific antisera raised against the α subunit of G proteins Gi1, Gi1-2, Gi3, and Gs. Differences in G-protein expression were quantified by densitometry and expressed as percentage change from normal controls. The expression of Giα1 was significantly increased in 80% of tumors (Giα1, 284% ± 77%; P <.05 percent of normal tissue), whereas Giα1-2 and Giα3 expression was increased in 67% of tumors (Giα1-2, 218% ±21%; Giα3, 154% ± 6%; P <.05 percent of normal tissue). The functional activity of Giα proteins as determined by pertussis toxin-catalyzed adenosine diphosphate (ADP)- ribosylation was also significantly increased in these tumors. In contrast, Gsα-protein expression was significantly reduced in all tumors examined (74% ± 8% of normal tissue, P <.05). The functional activity of Gsα, as determined by adenylyl cyclase (AC) activity, was significantly decreased in tumor as compared to normal liver under both basal and agonist stimulated (guanosine triphosphate γ S and forskolin) conditions. In summary, these data show for the first time a significant alteration in G-protein expression and functional activity in human HCC tissue. These alterations indicate a down-regulation of the AC-linked enzyme effector system in HCC that may be of critical importance to the formation and progression of human hepatocellular carcinoma.

Original languageEnglish (US)
Pages (from-to)1189-1194
Number of pages6
JournalHepatology
Volume26
Issue number5
StatePublished - Nov 1997
Externally publishedYes

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GTP-Binding Proteins
Human Activities
Hepatocellular Carcinoma
Neoplasms
Adenylyl Cyclases
Proteins
Densitometry
Liver
Pertussis Toxin
Colforsin
Guanosine Triphosphate
Adenosine Diphosphate
Immune Sera
Down-Regulation
Western Blotting
Enzymes
Growth

ASJC Scopus subject areas

  • Hepatology

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Alterations in guanine nucleotide regulatory protein expression and activity in human hepatocellular carcinoma. / Schmidt, C.; Mckillop, Iain H.; Cahill, Paul A.; Sitzmann, James V.

In: Hepatology, Vol. 26, No. 5, 11.1997, p. 1189-1194.

Research output: Contribution to journalArticle

Schmidt, C. ; Mckillop, Iain H. ; Cahill, Paul A. ; Sitzmann, James V. / Alterations in guanine nucleotide regulatory protein expression and activity in human hepatocellular carcinoma. In: Hepatology. 1997 ; Vol. 26, No. 5. pp. 1189-1194.
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abstract = "Alterations in the expression and activity of guanine nucleotide regulatory proteins (G proteins) have been linked to the growth of several human tumors. We hypothesized that the expression and activity of G proteins are altered in human hepatocellular carcinoma (HCC). The expression of Gi and Gs proteins was determined in six human tumors and six normal controls (adjacent nonneoplastic liver) by Western blotting using specific antisera raised against the α subunit of G proteins Gi1, Gi1-2, Gi3, and Gs. Differences in G-protein expression were quantified by densitometry and expressed as percentage change from normal controls. The expression of Giα1 was significantly increased in 80{\%} of tumors (Giα1, 284{\%} ± 77{\%}; P <.05 percent of normal tissue), whereas Giα1-2 and Giα3 expression was increased in 67{\%} of tumors (Giα1-2, 218{\%} ±21{\%}; Giα3, 154{\%} ± 6{\%}; P <.05 percent of normal tissue). The functional activity of Giα proteins as determined by pertussis toxin-catalyzed adenosine diphosphate (ADP)- ribosylation was also significantly increased in these tumors. In contrast, Gsα-protein expression was significantly reduced in all tumors examined (74{\%} ± 8{\%} of normal tissue, P <.05). The functional activity of Gsα, as determined by adenylyl cyclase (AC) activity, was significantly decreased in tumor as compared to normal liver under both basal and agonist stimulated (guanosine triphosphate γ S and forskolin) conditions. In summary, these data show for the first time a significant alteration in G-protein expression and functional activity in human HCC tissue. These alterations indicate a down-regulation of the AC-linked enzyme effector system in HCC that may be of critical importance to the formation and progression of human hepatocellular carcinoma.",
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