Elevated levels of ERK2 in human breast carcinoma MCF‐7 cells transfected with protein kinase Cα

Abstract

We investigated the effect of elevated levels of protein kinase C alpha (PKC alpha) on cell proliferation in human breast carcinoma cells (MCF-7). MCF-7 cells transfected with either the pSV2M(2)6 vector without the insert (MCF-7/Vector) or containing a full length cDNA encoding PKC alpha (MCF-7/PKC alpha) were compared. MCF-7/PKC alpha cells were found to have an increased proliferative rate with a doubling time of 15 h as compared to 42 h for MCF-7/Vector cells. Flow cytometry illustrated a greater percentage of MCF-7/PKC alpha cells in the S phase of the cell cycle. Western and Northern blot analyses demonstrated an increase in extracellular regulated protein kinase 2 (ERK2) gene expression in MCF-7/PKC alpha cells but no alteration of this gene expression in MCF-7/Vector cells. These results suggested that the elevated level of ERK2 which is also known as mitogen activated protein kinase is probably involved in the increase in MCF-7/PKC alpha cell proliferation.

Berberine Suppresses the TPA-Induced MMP-1 and MMP-9 Expressions Through the Inhibition of PKC-α in Breast Cancer Cells

“…In particular, the PKC-a levels may be increased in breast cancer patients with low or negative estrogen receptor (ER) levels, and the PKC-a levels are inversely associated with the ER levels in breast cancer [30,31]. Cell proliferation by PKC-a overexpression showed a shortened doubling time in MCF7 breast cancer cells compared with that of their parental cells [32]. This increased cell proliferation rate was involved with the activation of the PKC-a/ERK2 pathway [32].…”

Isoform-specific and Protein Kinase C-mediated Regulation of CTP:Phosphoethanolamine Cytidylyltransferase Phosphorylation

“…PMA-resistant cells have an impaired PE synthesis and Pcyt2 activity (34,35), and phorbol esters target two different PKC isozymes in MCF-7 cells, PKC-␤I/II for the stimulation of PE synthesis and PKC␣ for the stimulation of PE degradation (8). PKC␣ has been strongly implicated in breast cancer development (29). We provided evidence that part of the cancer cell defense mechanism against unfavorable growth conditions of serum deficiency includes the stimulation of Pcyt2␣ activity by phosphorylation and increased membrane PE synthesis (1).…”

“…Pcyt2␣ Mutants Do Not Support Cell Growth-Regulation of Pcyt2 activity by PKC␣, also an important marker of breast cancer cell proliferation (29), suggests that the stimulation of Pcyt2␣ and PE synthesis under serum deficiency (1) is important in supporting the cancer cell growth and survival. To test if the Pcyt2␣ mutants could influence the MCF-7 cell growth, the cells were transfected with wild-type or the phosphorylation site mutants described above, and cell growth was monitored under serum-deficient conditions.…”

Protein Kinase C Alpha Expression in Breast and Ovarian Cancer

“…MCF-7 breast cancer cells transfected with PKC-α showed a shortened doubling time compared to their parental control (15 vs. 42 h). This increased proliferation was associated with increased levels of Erk2 [42]. In contrast to this observation, nonmetastatic human mammary epithelial breast cancer MCF-10A cells when transfected with a high-level PKC-α-expressing clone showed a lengthened doubling time [43].…”