Biomedical subjects

Karina B Falbo

Publications and source records attributed to Karina B Falbo.

3 recordsLinked to original sources

PubMed2007

Protein kinase C delta enhances proliferation and survival of murine mammary cells.

Protein kinase C (PKC) delta, a member of the novel family of PKC serine-threonine kinases, has been implicated in negative regulation of proliferation and apoptosis in a large number of cell types, including breast cancer cell lines, and postulated as a tumor suppressor gene. In this study we show that in murine NMuMG mammary cells PKCdelta promotes a mitogenic response. Overexpression of PKCdelta in NMuMG cells leads to a significant increase in [3H]-tymidine incorporation and cell proliferation, as well as enhanced extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) activation. Activation of PKCdelta with a phorbol ester leads to elevated cyclin D1 expression and an hyperphosphorylated Rb state. Surprisingly, ectopic expression of PKCdelta conferred anchorage-independent growth capacity to NMuMG cells. PKCdelta overexpressors showed enhanced resistance to apoptotic stimuli, such as serum deprivation or doxorubicin treatment, an effect that correlates with hyperactivation of the Akt survival pathway. Our results provide evidence for a role of PKCdelta as a positive modulator of proliferative and survival signals in immortalized mammary cells. The fact that PKCdelta exerts differential responses depending on the cell context not only highlights the necessity to carefully understand the signaling events controlled by this PKC in each cell type but also suggests that we should be cautious in considering this kinase a target for cancer therapy.

Animals↗

PubMed2006

Chromatin remodeling in DNA replication.

Chromatin remodeling complexes have evolved to solve a very basic problem for eukaryotic cells accommodation of the genome to fit the dimensions of the nucleus without loss of access to the DNA molecule. In the nucleus, DNA is wrapped around histones to form nucleosomes and other higher order compact chromatin structures. Chromatin remodeling complexes enable highly regulated access to DNA sequences in the context of chromatin, and it is well known that these complexes are involved in regulation of transcription. However, gene expression is not the only process that occurs in the nucleus. DNA has to be replicated, recombined, and repaired. In this regard, it is notable that the recent discoveries have linked ATP-dependent remodeling complexes to DNA damage repair. These results have raised challenging questions about the possible versatility of chromatin remodeling complexes in other nuclear activities, particularly in DNA replication, since a number of recent studies have suggested a connection between this essential cellular process and chromatin remodeling. However, the chromatin remodeling events regulating DNA replication have not been extensively investigated. The aim of this prospect is to summarize recent studies that implicate chromatin remodeling in DNA replication and to address potential roles of chromatin remodeling at various stages of eukaryotic DNA replication.

Adenosine Triphosphate↗

PubMed2005

Atypical protein kinase C-zeta modulates clonogenicity, motility, and secretion of proteolytic enzymes in murine mammary cells.

In this paper, we investigated whether protein kinase C-zeta (PKC zeta), a member of the atypical PKC family, induces phenotypic alterations associated with malignant transformation and tumor progression in mammary cells. The stable overexpression of PKC zeta in immortalized mammary epithelial cells (NMuMG), activates the mitogenic extracellular signal-regulated kinase (ERK) pathway, enhanced clonal cell growth and exerts profound effects on proteases secretion. The effect on proteases expression seems to be specific for urokinase-type plasminogen activator and metalloproteinase-9 (MMP-9) because no modulation in MMP-2 and MMP-3 production could be detected. In addition, our experiments demonstrated that PKC zeta overexpression markedly altered the adhesive, spreading, and migratory abilities of NMuMG cells. The overexpression of this enzyme was not sufficient to confer an anchorage-independent growth capacity. An extensive mutational analysis of PKC zeta revealed that the effects observed in NMuMG cells were strictly dependent on the kinase (catalytic) domain of the enzyme. Taken together, these results suggest that in mammary cells PKC zeta modulates several of the critical events involved in tumor development and dissemination through the activation of mitogen activated protein kinase (MAPK)/ERK pathway.

Animals↗