Endocrine Abstracts (2008) 16 P279

PTHrP and HRG outcomes in MCF7 breast cancer cells transfected with HER receptors gene

Majed Alokail


Biochemistry Department, College of Science #5, King Saud University, Riyadh, Saudi Arabia.


Metastasis to bone occurs frequently in advanced breast cancer and is accompanied by debilitating skeletal complications. Parathyroid hormone-related protein (PTHrP) occurs in a high proportion of breast cancer and is strongly implicated in their metastatic spread to bone. Overexpression of PTHRP and its receptor in breast tumour cells could also promote the growth in an autocrine fashion. Signal transduction of growth factor receptor, EGFR (ErbB1, HER1) and ErbB2 (Neu, HER2) receptor has been implicated in conferring resistance to traditional chemotherapy on cancer cells. Activation of extracellular-regulated kinase/mitogen-activated protein kinase (Erk/MAPK) is a critical signal transduction event-mediated cell proliferation, cell migration and tumor progression. In the present study, we examined the role of PTHrP-1-34, PTHrP-7-34 and PTHrP-1-86 in the Erk pathway in MCF7 breast carcinoma cell line with or without heregulinbeta1 (HRG beta1). MCF7 were transfected with pcDNA3/EGFR or with pcDNA3/erbB2 and treated overnight with 10 nM of PTHrP-1-34, PTHrP-7-34, or PTHrP-1-86 and for 30 min with 10 ng of HRGbeta1 in serum free medium. PTHrP-1-34 significantly overexpressed ErbB1 and ErbB2 receptors compared with PTHrP-7-34 and PTHrP-1-86 treatment. Erk activity was significantly enhanced with HRG beta1 and PTHrP-1-34. But with PTHrP-7-34 and PTHrP-1-86, Erk activity was less significantly enhanced. Moreover, the level of protein kinase C, PKC found to be much higher with PTHrP-1-34 than PTHrP-7-34 and PTHrP-1-86 treated cells. However, the PKC was demolished in HRG beta1 treated cells and PKC activation had no effect on erbB1 and erbB2 induced Erk activation. Our results conclude that cross-talk between PTHrP receptor and ErbB1 and erbB2 receptors could be crucial growth-promoting effects in tumor progression.

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