Intermediate Ca2+-Sensitive K+ Channels are Necessary for Prolactin-Induced Proliferation in Breast Cancer Cells |
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Authors: | Malika Faouzi Valérie Chopin Ahmed Ahidouch Halima Ouadid-Ahidouch |
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Institution: | 1. Laboratoire de Physiologie Cellulaire et Moléculaire, JE 2530, Université de Picardie Jules Verne, 33 rue St. Leu, 80000, Amiens, France 2. Laboratoire de Physiologie Animale, Université Ibn-Zohr, Agadir, Morocco
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Abstract: | Prolactin (PRL) is a polypeptidic hormone which acts both systemically and locally to cause lactation by interacting with
the PRL receptor, a Janus kinase (JAK2)-coupled cytokine receptor family member. Several studies have reported that serum
PRL level elevation is associated with an increased risk for breast cancer, and evidence has suggested that PRL is one actor
in the pathogenesis and progression of this cancer. We previously reported the involvement of hIKCa1 in breast cell cycle
progression and cell proliferation. However, mechanisms by which PRL cooperates with these channels to modulate breast epithelial
cell proliferation remain unknown. Our results showed that, in the MCF-7 breast cancer cell line, PRL increased hIKCa1 current
density. These channels were functional and regulated the resting membrane potential. The PRL effects were inhibited by TRAM-34
and clotrimazole, the most used hIKCa1 blockers. Moreover, PRL increased proliferation in a dose-dependent manner without
overexpressing hIKCa1. To determine whether PRL-induced proliferation and hIKCa1 activity involved the JAK2 pathway, we used
pharmacological JAK2 inhibitors (AG490 and JAK inhibitor I). Indeed, PRL-induced JAK2 phosphorylation was required for both
cell proliferation and hIKCa1 activity. In the presence of either hIKCa1 blockers or siRNA-hIKCa1, PRL failed to increase
cell proliferation and hIKCa1 activity. Taken together, our results demonstrate that PRL plays a role in breast cancer cell
proliferation by increasing hIKCa1 activity through the JAK2 signaling pathway. |
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