The Phosphoprotein StarD10 Is Overexpressed in Breast Cancer and Cooperates with ErbB Receptors in Cellular Transformation

Abstract

We have identified that StarD10, a member of the START protein family, is overexpressed in both mouse and human breast tumors. StarD10 was initially discovered on the basis of its cross-reactivity with a phosphoserine-specific antibody in mammary tumors from Neu/ErbB2 transgenic mice and subsequently isolated from SKBR3 human breast carcinoma cells using a multistep biochemical purification strategy. We have shown that StarD10 is capable of binding lipids. StarD10 was found to be overexpressed in 35% of primary breast carcinomas and 64% of human breast cancer cell lines, correlating with their ErbB2/Her2 status. Coexpression of StarD10 with ErbB1/epidermal growth factor receptor in murine fibroblasts enhanced anchorage-independent growth in soft agar, providing evidence for functional cooperation between StarD10 and ErbB receptor signaling. Taken together, these data suggest that overexpression of this lipid-binding protein contributes to breast oncogenesis.

Loss of STARD10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative status

“…Sections, without antigen retrieval, were incubated with a 1:100 dilution of an affinity purified rabbit anti-STARD10 antibody, 15 and detection was performed with EnvisionþRabbit (DAKO) for 30 min at room temperature followed by visualization using DABþ (DAKO) for 5 min. Slides were also stained using the following monoclonal antibodies: ER 1:100 (6F11, DAKO), PR 1:200 (PgR-636, DAKO).…”

XIAP-deficiency leads to delayed lobuloalveolar development in the mammary gland

“…(c) Protein lysates from mammary glands of wild-type (WT) and XIAP knock-out (KO) mice were subjected to SDS-PAGE and immunoblotted using anti-XIAP monoclonal antibody (MBL, Nagoya, Japan). 15 Proteins were visualized with peroxidase-coupled secondary antibody using the ECL detection system. Equal loading was confirmed by reprobing with an a-tubulin-specific antibody (Sigma).…”

The mammalian START domain protein family in lipid transport in health and disease

“…STARD10 was identified as a 35 kDa anti-phospho-FKHR immunoreactive band that was overexpressed in tumors of ErbB2 transgenic mice (Olayioye et al 2004). Recombinant purified STARD10 specifically extracts PC and PE from reconstituted lipid vesicles and enhances PC and PE transfer from donor to acceptor vesicles in vitro (Olayioye et al 2005).…”

“…STARD10: a phosphatidylcholine/ethanolamine-binding protein in breast cancer STARD10 was originally reported to be co-expressed with ErbB2/HER2/neu in breast cancer cell lines and primary breast carcinomas (Olayioye et al 2004). Functionally, the overexpression of STARD10 in NIH-3T3 fibroblast cells promoted anchorage-independent cell growth only if expressed together with ErbB2, suggesting that STARD10 may function within the ErbB2/HER2/neu receptor signaling pathway (Olayioye et al 2004).…”

“…Functionally, the overexpression of STARD10 in NIH-3T3 fibroblast cells promoted anchorage-independent cell growth only if expressed together with ErbB2, suggesting that STARD10 may function within the ErbB2/HER2/neu receptor signaling pathway (Olayioye et al 2004). However, STARD10 and HER2/neu mRNA and protein expression levels were later shown to be inversely correlated when analyzed in breast tumors from a large cohort of patients (Murphy et al 2009).…”