Heregulinbeta activates store-operated Ca2+ channels through c-erbB2 receptor level-dependent pathway in human breast cancer cells.
The heregulinbeta (HRGbeta) is a ligand to activate c-erbB2/c-erbB3 interaction and can subsequently increases cytosolic [Ca(2+)](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, HRGbeta induced Ca(2+) release from the endoplasmic reticulums (ER) and subsequently activated Ca(2+) entry via store-operated Ca(2+) channel (SOC). However, in SK-BR-3, HRGbeta failed to induce Ca(2+) release and Ca(2+)entry. RNA interference to decrease c-erbB2 level in SK-BR-3 resulted in reactivation of HRGbeta-evoked Ca(2+) release and Ca(2+) entry via SOC, which was similar to that of MCF-7. In addition, in the absence of HRGbeta, 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 [Ca(2+)](i) responses to HRGbeta. In SK-BR-3, the Ca(2+) mobilization in the presence or in the absence of HRGbeta was completely blocked by PLC inhibitor U73122. In summary, our results indicate that HRGbeta-induced SOC was regulated by c-erbB2 level and dependent on activation of PLC in human breast cancer cells.
Liao
Jie-Ying
JY
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Li
Lin-Lin
LL
Wei
Qun
Q
Yue
Jia-Chang
JC
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D045744:Cell Line, Tumor; D003600:Cytosol / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020890:Neuregulin-1 / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D002118:Calcium; D015220:Calcium Channels; D020890:Neuregulin-1; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D010738:Type C Phospholipases