Heregulinβ activates store-operated Ca²⁺ channels through c-erbB2 receptor level-dependent pathway in human breast cancer cells

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• 作者：Jie-Ying Liao ; Lin-Lin Li ; Qun Wei ; Jia-Chang Yue
• 关键词：HRGβ ; Store-operated Ca²⁺ channel (SOC) ; C-erbB2 ; PLC ; Human breast cancer cells
• 刊名：Archives of Biochemistry and Biophysics
• 出版年：2007
• 期刊代码：116_00039861
• 类别：ch
• 出版时间：15 February 2007
• 卷：458
• 期：2
• 页码：244-252
• 文件大小：597 K

摘要

The heregulinβ (HRGβ) is a ligand to activate c-erbB2/c-erbB3 interaction and can subsequently increases cytosolic [Ca²⁺]_i. In the two human breast cancer cell lines, MCF-7 shows a low c-erbB2 expression level, whereas SK-BR-3 overexpress c-erbB2 receptor. In this article, we have found that in MCF-7, HRGβ induced Ca²⁺ release from the endoplasmic reticulums (ER) and subsequently activated Ca²⁺ entry via store-operated Ca²⁺ channel (SOC). However, in SK-BR-3, HRGβ failed to induce Ca²⁺ release and Ca²⁺entry. RNA interference to decrease c-erbB2 level in SK-BR-3 resulted in reactivation of HRGβ-evoked Ca²⁺ release and Ca²⁺ entry via SOC, which was similar to that of MCF-7. In addition, in the absence of HRGβ, a constitutive activation of SOC was observed in SK-BR-3 rather than in MCF-7 and c-erbB2-siRNA treated SK-BR-3. Compared to the cells with low c-erbB2 level, c-erbB2 might tend to interact with c-erbB3 in the resting state in the cells with high c-erbB2 level, which resulted in different [Ca²⁺]_i responses to HRGβ. In SK-BR-3, the Ca²⁺ mobilization in the presence or in the absence of HRGβ was completely blocked by PLC inhibitor U73122. In summary, our results indicate that HRGβ-induced SOC was regulated by c-erbB2 level and dependent on activation of PLC in human breast cancer cells.