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Pkc Inhibition Increases Gap Junction Intercellular Communication And Cell Adhesion In Human Neuroblastoma, M. Morley, C. Jones, M. Sidhu, V. Gupta, S. Bernier, W. Rushlow, Daniel Belliveau
Pkc Inhibition Increases Gap Junction Intercellular Communication And Cell Adhesion In Human Neuroblastoma, M. Morley, C. Jones, M. Sidhu, V. Gupta, S. Bernier, W. Rushlow, Daniel Belliveau
Daniel J. Belliveau
Abstract Gap junction intercellular communication and cell–cell adhesion are essential for maintaining a normal cellular phenotype, including the control of growth and proliferation. Loss of either cell–cell adhesion or communication is common in cancers, while restoration of function is associated with tumor suppression. Protein kinase C (PKC) isozymes regulate a broad spectrum of cellular functions including growth and proliferation, and their overexpression has been correlated with carcinogenesis. Consequently, PKC inhibitors are currently undergoing clinical trials as an anti-cancer agents although the precise cellular alterations induced by PKC inhibitors remain to be elucidated. In the current study, the effects of PKC …
Connexin Overexpression Differentially Suppresses Glioma Growth And Contributes To The Bystander Effect Following Hsv-Thymidine Kinase Gene Therapy, T. Jiminez, W. Fox, C. Naus, J. Galipeau, Daniel Belliveau
Connexin Overexpression Differentially Suppresses Glioma Growth And Contributes To The Bystander Effect Following Hsv-Thymidine Kinase Gene Therapy, T. Jiminez, W. Fox, C. Naus, J. Galipeau, Daniel Belliveau
Daniel J. Belliveau
Neoplastic transformation is frequently associated with a loss of gap junctional intercellular communication and reduced expression of connexins. The introduction of connexin genes into tumor cells reverses the proliferative characteristics of such cells. However, there is very little comparative information on the effects of different connexins on cancer cell growth. We hypothesized that Cx26, Cx32, or Cx43 would display differential growth suppression of C6 glioma cells and uniquely modulate the bystander effect following transduction of C6 cells with HSVtk followed by suicide gene therapy. The bystander phenomenon is the death of a greater number of tumor cells than are expressing …
Retroviral Delivery Of Connexin Genes To Human Breast Tumor Cells Inhibits In Vivo Tumor Growth By A Mechanism That Is Independent Of Significant Gap Junctional Intercellular Communication, H. Qin, Q. Shao, H. Curtis, J. Galipeau, Daniel Belliveau, T. Wang, M. Alaoui-Jamali, D. Laird
Retroviral Delivery Of Connexin Genes To Human Breast Tumor Cells Inhibits In Vivo Tumor Growth By A Mechanism That Is Independent Of Significant Gap Junctional Intercellular Communication, H. Qin, Q. Shao, H. Curtis, J. Galipeau, Daniel Belliveau, T. Wang, M. Alaoui-Jamali, D. Laird
Daniel J. Belliveau
The mechanism by which gap junction proteins, connexins, act as potent tumor suppressors remains poorly understood. In this study human breast tumor cells were found to exhibit diverse gap junction phenotypes including (a) undetectable Cx43 and no intercellular communication (HBL100); (b) low levels of Cx43 and sparse intercellular communication (MDA-MB-231); and (c) significant levels of Cx43 and moderate intercellular communication (Hs578T). Although retroviral delivery of Cx43 and Cx26 cDNAs to MDA-MB-231 cells did not achieve an expected substantial rescue of intercellular communication, overexpression of connexin genes did result in a dramatic suppression of tumor growth when connexin-expressing MDA-MB-231 cells were …
Aggregated Dsred-Tagged Cx43 And Over-Expressed Cx43 Are Targeted To Lysosomes In Human Breast Cancer Cells, H. Qin, Q. Shao, Daniel Belliveau, D. Laird
Aggregated Dsred-Tagged Cx43 And Over-Expressed Cx43 Are Targeted To Lysosomes In Human Breast Cancer Cells, H. Qin, Q. Shao, Daniel Belliveau, D. Laird
Daniel J. Belliveau
To investigate if either wild-type or aggregated Cx43 is abnormally targeted to lysosomes in human breast tumor cells, we examined the fate of DsRed-tagged Cx43 and over-expressed Cx43 in communication-deficient HBL-100 and MDA-MB-231 cells. DsRed-tagged Cx43 was assembled into gap junctions in control normal rat kidney cells that express endogenous Cx43 but not in Cx43-negative HBL-100 cells. However, when HBL-100 cells were engineered to coexpress wild-type Cx43 a population of DsRed-tagged Cx43 was rescued and assembled into gap junctions. Co-expression of wild-type Cx26 failed to rescue the assembly of DsRed-tagged Cx43 into gap junctions. Immunolocalization studies revealed that DsRed-tagged Cx43 …
In Vivo Growth Of C6 Glioma Cells Transfected With Connexin43 Cdna, C. Naus, K. Elisevich, D. Zhu, Daniel Belliveau, R. Del Maestro
In Vivo Growth Of C6 Glioma Cells Transfected With Connexin43 Cdna, C. Naus, K. Elisevich, D. Zhu, Daniel Belliveau, R. Del Maestro
Daniel J. Belliveau
In order to examine the possible role of intercellular communication via gap junctions in the control of tumor growth, we have transfected C6 glioma cells with connexin43 cDNA. We obtained several clones with variable expression of connexin43. The growth rate of these clones in culture was inversely related to the degree of expression of the transfected cDNA. To examine the growth of these transfected cells in vivo, cells were grown in spinner culture flasks to form spheroids 250–300 µm in diameter. Spheroids of nontransfected C6 cells produced large gliomas. Immunohistochemical and in situ hybridization analyses revealed relatively high levels of …