Effect of a mammary‐derived growth inhibitor on the expression of the oncogenes c‐fos, c‐myc and c‐ras

Lehmann, Wolfram; Strauß, Michael; Kießling, U.; Graetz, H; Koberling, A.; Langen, P.

doi:10.1016/0014-5793(89)81189-5

Cited by 3 publications

(1 citation statement)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MDGI is a nuclear protein that is maximally expressed in terminally differentiated mammary tissue (35) and has inhibitory activity on the growth of different breast cancer cell lines (36), reducing the transcriptional expression of c-fos, c-myc, and c-ras and suppressing the mitogenic effects of EGF (37). Nuclear translocation of HRGh 1 is correlated with c-myc induction (13); however, further investigations are needed to understand the functional effect of the protein interaction between MDGI and HRGa 1-241 on growth response and cell differentiation.…”

Section: Hrga 1-241 Interacts With Nuclear Proteinsmentioning

confidence: 99%

Heregulins Implicated in Cellular Functions Other Than Receptor Activation

Breuleux¹,

Schoumacher²,

Rehn³

et al. 2006

Molecular Cancer Research

View full text Add to dashboard Cite

Heregulins (HRG) are known as soluble secreted growth factors that, on binding and activating ErbB3 and ErbB4 cell surface receptors, are involved in cell proliferation, metastasis, survival, and differentiation in normal and malignant tissues. Previous studies have shown that some HRG1 splice variants are translocated to the nucleus. By investigating the subcellular localization of HRGA 1-241 , nuclear translocation and accumulation in nuclear dot-like structures was shown in breast cancer cells. This subcellular distribution pattern depends on the presence of at least one of two nuclear localization sequences and on two domains on the HRG construct that were found to be necessary for nuclear dot formation. Focusing on the nuclear function of HRG, a mammary gland cDNA library was screened with the mature form of HRGA in a yeast two-hybrid system, and coimmunoprecipitation of endogenous HRG was done. The data reveal positive interactions of HRGA 1-241 with nuclear factors implicated in different biological functions, including transcriptional control as exemplified by interaction with the transcriptional repressor histone deacetylase 2. In addition, HRGA 1-241 showed transcriptional repression activity in a reporter gene assay. Furthermore, a potential of HRG proteins to form homodimers was reported and the HRG sequence responsible for dimerization was identified. These observations strongly support the notion that HRG1 splice variants have multifunctional properties, including previously unknown regulatory functions within the nucleus that are different from the activation of ErbB receptor signaling.

show abstract

Section: Hrga 1-241 Interacts With Nuclear Proteinsmentioning

confidence: 99%