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Figure 1 | Breast Cancer Research

Figure 1

From: Key signalling nodes in mammary gland development and cancer: Myc

Figure 1

Ins and outs of the 'black box' MYC during normal mammary gland development. The diagram displays the models (italic, top) used to investigate the various inputs and outputs of Myc (green boxes). Speculations based on other model systems that have not yet been shown in the mammary gland are presented in red. Inputs are signaling molecules that are known or suggested to impact on Myc levels; inputs are not applicable (n.a.) in transgenic models with genetically deregulated Myc levels. The outputs are, where available, direct targets of Myc transcriptional activity and general biological functions described for Myc at the specific developmental stage (italic, bottom). During embryogenesis, transgenic expression of Neuregulin3 (Nrg3), a major factor controlling mammary placode development, induced high Myc levels, thereby changing the proliferative and adhesive properties of cells [11]. The speculated role of Myc in mammary stem cells (SCs) is mostly based on data from hematopoietic SCs and the known importance of Wnt and Notch pathways in other SC types [13]. Myc's role during puberty and early pregnancy has not yet been analyzed, but as various steroids and paracrine factors can induce its expression [3] Myc might play a role in promoting proliferation and cell growth via its numerous cell cycle and translation-related targets. A transgenic mouse model (MMTV-rtTA/TetO-MYC (MTB/TOM)) revealed that Myc overexpression during late pregnancy leads to precocious proliferation and differentiation via repression of Caveolin1 (Cav1) and signal transducer and activator of transcription (Stat) 5 hyperactivation [27]. Despite its low levels during lactation, Myc has an important role in mRNA translation, as shown in our own laboratory using mammary glands conditionally lacking Myc (Myc-CKO) [29]. Finally, in Socs3 conditional knockout (CKO) mice it was shown that increased Stat3 activation leads to accelerated apoptosis via high levels of Myc, suggesting a direct role for Myc downstream of Stat3 in involution [31]. More detailed discussion can be found in the text. K14, Keratin14; KO, knockout; N-Cad, N-cadherin.

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