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Table 1
Cell culture based experimental characterisation of ERK1/2 association with breast cancer pregression
	Model	Reference

ERK1/2 signalling
MEK1 signalling mediates transformation and metastasis	EpH4 mammary epithelial cells	[25]
RAF/MEK/ERK1/2 and PI3K/PTEN/AKT signalling pathways interact in breast cancer	Hematopoietic, breast (MCF7) and prostate cancer cells	[22]

Three-dimensional organisation
MECs fail to organise as acini because of a persistent β1-integrin-EGFR-ERK1/2 drive, but will form acini if β1-integrin, EGFR or ERK1/2 function is inhibited	HMT-3522 T-42	[75]
Persistent activation of ERK1/2 impairs acinus formation and leads to invasion	HC11 MECs	[34]
Delayed activation of ERK1/2 impacts cell proliferation and ERα-mediated transcription	MCF7	[82]
Over-expressed Par6 acts in a complex with cdc42 and aPKC to induce hyperproliferation and generate multi-acinar structures in an ERK1/2-dependent fashion	MECs	[36]
Activation of the ERK1/2 blocks Bim expression and correlates with protection from luminal apoptosis	MECs	[37]

Invasion
Ha-Ras cooperates with TGFβ to induce EMT and Raf/ERK1/2 is required	Ha-Ras-transformed MECs in 3D collagen/matrigel matrices	[40]
ERK1/2 signalling induces MMP expression and the duration of MAPK activation is an important determinant for certain growth factor-mediated functions	Keratinocytes	[53]
uPA binding to uPAR activates ERK1/2 and induces cell migration	MCF7	[8]
uPA induces cell proliferation via ERK1/2 activation	MDA-MB-231	[56]
uPA determines the basal level of activated ERK1/2 and prevents apoptosis	MDA-MB-231	[57]
Restoration of an epithelial phenotype requires both the over-expression of E-cadherin and the suppression of ERK1/2	MCF10A cells over-expressing activated Ras	[64]
Scribble co-operates with mutations in Ras and Raf to induce a migratory phenotype via induction of ERK1/2	MCF10A	[67]
ECM changes impact integrin signalling and can promote mitogenic signalling through ERK1/2	Non-malignant and human breast tumour cell line (T4-2)	[75]
ERK1/2 substrates, the Ets transcription factors, induce EMT and invasiveness	MECs	[76-78]
'Tumour-initiating cells' can be derived from mammary cells following the activation of ERK1/2 and induction of EMT	MECs	[81]

ErbB/EGFR signalling to ERK1/2
Overexpression of ErbB2 induces EMT through ERK1/2 activation	MCF10A	[90]
Expression of ErbB2 induces anti-apoptotic proteins Survivin and Bcl-2 via ERK1/2 and PI3K signalling	MCF7	[87]
Experimentally triggered ErbB2 activation protects against apoptosis and disrupts mammary epithelial cell organisation in an ERK1/2-dependent manner	MCF10A	[88,89]
Progesterone receptor, IGF-1, VEGF, growth hormone and a range of ligands require EGFR to induce ERK1/2 activation	T47D, MECs	[91]

ER, tamoxifen resistance and ERK1/2 signalling
ERK1 and 2 are activated via oestrogen signalling through GPR30, resulting in transactivation of EGFR	MCF7, SKBR3 breast cancer cells	[10]
EGFR or ErbB2 resistance correlated with high ERK1/2 and AKT activity	Breast cancer cells	[9]

Cell survival and cell death
Survival factor-induced ERK1/2 phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity	Haematopoietic cells	[134]
ERK1/2 phosphorylates the pro-apoptotic BCL-2 family member Bim_EL, leading to its degradation by the proteasome	CC139 fibroblasts	[132,133]

aPKC = atypical PKC; EGF = epidermal growth factor; EGFR = EGF receptor; EMT = epithelial-to-mesenchymal transition; ER = oestrogen receptor; ERK = extracellular regulated kinase; IGF = insulin-like growth factor; MAPK = mitogen-activated protein kinase; MEC = mammary epithelial cell; MMP = matrix-metalloproteinase; Par = Partitioning defect; PI3K = phosphoinositide 3-kinase; PTEN, phosphatase and tensin homolog; TGF = transforming growth factor; uPA = Plasminogen activator, Urokinase; uPAR = Urokinase receptor; VEGF = vascular epidermal growth factor.
Whyte et al. Breast Cancer Research 2009 11:209 doi:10.1186/bcr2361

Table 1