Neoplastic phenotype of gap-junctional intercellular communication- deficient WB rat liver epithelial cells and its reversal by forced expression of connexin 32

Robert S. Rae, Parmender P. Mehta, Chia Cheng Chang, James E. Trosko, Randall J. Ruch

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Gap-junctional intercellular communication (GJIC) is involved in cellular growth control and is often reduced in neoplastic cells. In this study, four GJIC-deficient rat liver epithelial cell lines (WB-aB1, WB-bA2, WB-cD6, and WB-dA2) were examined for altered growth and tumorigenicity in comparison with their GJIC-competent parental cell line, WB-F344. WB-aB1 cells were also forced to express connexin 32 (Cx32) by transduction with a Cx32 cDNA retroviral expression vector to help determine whether the restoration of GJIC could reverse their neoplastic phenotype. WB-aB1 and WB- bA2 cells had faster population doubling times (PDTs) and higher saturation densities (SDs) than did WB-F344 cells. In contrast, the growth of WB-cD6 and WB-dA2 cells was not significantly different from that of WB-F344 cells. WB- aB1 and WB-bA2 cells formed tumors in male F344 rats, but WB-cD6 and WB-dA2 cells did not. After transduction of WB-aB1 cells with Cx32, four stable clones (WB-a/32-3, -8, -9, and -10) were isolated that had GJIC levels of 5.2%, 44.5%, 69.8%, and 90.5%, respectively. The growth of poorly coupled clones 3 and 8 was similar to that of parental WB-aB1 cells, but the growth of well-coupled clones 9 and 10 was similar to that of WB-F344 cells. The tumorigenicity of WB-a/32-9 and WB-a/32-10 cells was also significantly lower than that of WB-aB1 cells. Our results suggest that reduced GJIC contributes to neoplastic transformation of WB cells, that additional changes are necessary, and that restoration of GJIC by forced Cx32 protein expression can suppress the neoplastic phenotype of these cells.

Original languageEnglish (US)
Pages (from-to)120-127
Number of pages8
JournalMolecular Carcinogenesis
Volume22
Issue number2
DOIs
StatePublished - Jun 1 1998

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Epithelial Cells
Phenotype
Liver
Growth
Clone Cells
connexin 32
Neoplastic Cell Transformation
Cell Line
Inbred F344 Rats
Complementary DNA

Keywords

  • Cell growth
  • Contact inhibition
  • Retrovirus
  • Transformation
  • Tumorigenicity

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Neoplastic phenotype of gap-junctional intercellular communication- deficient WB rat liver epithelial cells and its reversal by forced expression of connexin 32. / Rae, Robert S.; Mehta, Parmender P.; Chang, Chia Cheng; Trosko, James E.; Ruch, Randall J.

In: Molecular Carcinogenesis, Vol. 22, No. 2, 01.06.1998, p. 120-127.

Research output: Contribution to journalArticle

Rae, Robert S. ; Mehta, Parmender P. ; Chang, Chia Cheng ; Trosko, James E. ; Ruch, Randall J. / Neoplastic phenotype of gap-junctional intercellular communication- deficient WB rat liver epithelial cells and its reversal by forced expression of connexin 32. In: Molecular Carcinogenesis. 1998 ; Vol. 22, No. 2. pp. 120-127.
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abstract = "Gap-junctional intercellular communication (GJIC) is involved in cellular growth control and is often reduced in neoplastic cells. In this study, four GJIC-deficient rat liver epithelial cell lines (WB-aB1, WB-bA2, WB-cD6, and WB-dA2) were examined for altered growth and tumorigenicity in comparison with their GJIC-competent parental cell line, WB-F344. WB-aB1 cells were also forced to express connexin 32 (Cx32) by transduction with a Cx32 cDNA retroviral expression vector to help determine whether the restoration of GJIC could reverse their neoplastic phenotype. WB-aB1 and WB- bA2 cells had faster population doubling times (PDTs) and higher saturation densities (SDs) than did WB-F344 cells. In contrast, the growth of WB-cD6 and WB-dA2 cells was not significantly different from that of WB-F344 cells. WB- aB1 and WB-bA2 cells formed tumors in male F344 rats, but WB-cD6 and WB-dA2 cells did not. After transduction of WB-aB1 cells with Cx32, four stable clones (WB-a/32-3, -8, -9, and -10) were isolated that had GJIC levels of 5.2{\%}, 44.5{\%}, 69.8{\%}, and 90.5{\%}, respectively. The growth of poorly coupled clones 3 and 8 was similar to that of parental WB-aB1 cells, but the growth of well-coupled clones 9 and 10 was similar to that of WB-F344 cells. The tumorigenicity of WB-a/32-9 and WB-a/32-10 cells was also significantly lower than that of WB-aB1 cells. Our results suggest that reduced GJIC contributes to neoplastic transformation of WB cells, that additional changes are necessary, and that restoration of GJIC by forced Cx32 protein expression can suppress the neoplastic phenotype of these cells.",
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AU - Ruch, Randall J.

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AB - Gap-junctional intercellular communication (GJIC) is involved in cellular growth control and is often reduced in neoplastic cells. In this study, four GJIC-deficient rat liver epithelial cell lines (WB-aB1, WB-bA2, WB-cD6, and WB-dA2) were examined for altered growth and tumorigenicity in comparison with their GJIC-competent parental cell line, WB-F344. WB-aB1 cells were also forced to express connexin 32 (Cx32) by transduction with a Cx32 cDNA retroviral expression vector to help determine whether the restoration of GJIC could reverse their neoplastic phenotype. WB-aB1 and WB- bA2 cells had faster population doubling times (PDTs) and higher saturation densities (SDs) than did WB-F344 cells. In contrast, the growth of WB-cD6 and WB-dA2 cells was not significantly different from that of WB-F344 cells. WB- aB1 and WB-bA2 cells formed tumors in male F344 rats, but WB-cD6 and WB-dA2 cells did not. After transduction of WB-aB1 cells with Cx32, four stable clones (WB-a/32-3, -8, -9, and -10) were isolated that had GJIC levels of 5.2%, 44.5%, 69.8%, and 90.5%, respectively. The growth of poorly coupled clones 3 and 8 was similar to that of parental WB-aB1 cells, but the growth of well-coupled clones 9 and 10 was similar to that of WB-F344 cells. The tumorigenicity of WB-a/32-9 and WB-a/32-10 cells was also significantly lower than that of WB-aB1 cells. Our results suggest that reduced GJIC contributes to neoplastic transformation of WB cells, that additional changes are necessary, and that restoration of GJIC by forced Cx32 protein expression can suppress the neoplastic phenotype of these cells.

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