LXXLL peptide converts transportan 10 to a potent inducer of apoptosis in breast cancer cells.

Abstract	Degenerate expression of transcription coregulator proteins is observed in most human cancers. Therefore, in targeted anti-cancer therapy development, intervention at the level of cancer-specific transcription is of high interest. The steroid receptor coactivator-1 (SRC-1) is highly expressed in breast, endometrial, and prostate cancer. It is present in various transcription complexes, including those containing nuclear hormone receptors. We examined the effects of a peptide that contains the LXXLL-motif of the human SRC-1 nuclear receptor box 1 linked to the cell-penetrating transportan 10 (TP10), hereafter referred to as TP10-SRC1LXXLL, on proliferation and estrogen-mediated transcription of breast cancer cells in vitro. Our data show that TP10-SRC1LXXLL induced dose-dependent cell death of breast cancer cells, and that this effect was not affected by estrogen receptor (ER) status. Surprisingly TP10-SRC1LXXLL severely reduced the viability and proliferation of hormone-unresponsive breast cancer MDA-MB-231 cells. In addition, the regulation of the endogenous ERα direct target gene pS2 was not affected by TP10-SRC1LXXLL in estrogen-stimulated MCF-7 cells. Dermal fibroblasts were similarly affected by treatment with higher concentrations of TP10-SRC1LXXLL and this effect was significantly delayed. These results suggest that the TP10-SRC1LXXLL peptide may be an effective drug candidate in the treatment of cancers with minimal therapeutic options, for example ER-negative tumors.
Authors	Kairit Tints, Madis Prink, Toomas Neuman, Kaia Palm
Journal	International journal of molecular sciences (Int J Mol Sci) Vol. 15 Issue 4 Pg. 5680-98 (Apr 03 2014) ISSN: 1422-0067 [Electronic] Switzerland
PMID	24705462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CDK5RAP3 protein, human Cell Cycle Proteins Cell-Penetrating Peptides Estrogen Receptor alpha Estrogen Receptor beta Intracellular Signaling Peptides and Proteins Nerve Tissue Proteins Recombinant Fusion Proteins TFF1 protein, human Trefoil Factor-1 Tumor Suppressor Proteins transportan-10 NCOA1 protein, human Nuclear Receptor Coactivator 1
Topics	Amino Acid Motifs Apoptosis (drug effects) Breast Neoplasms (drug therapy, pathology) Cell Cycle Proteins Cell Line, Tumor Cell Proliferation (drug effects) Cell Survival (drug effects) Cell-Penetrating Peptides (genetics) Estrogen Receptor alpha (metabolism) Estrogen Receptor beta (metabolism) Female Gene Expression Regulation, Neoplastic (drug effects) Humans Intracellular Signaling Peptides and Proteins (genetics) MCF-7 Cells Nerve Tissue Proteins (genetics) Nuclear Receptor Coactivator 1 (genetics) Protein Binding Protein Structure, Tertiary Recombinant Fusion Proteins (genetics, pharmacology) Trefoil Factor-1 Tumor Suppressor Proteins (drug effects)

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