Steroid Receptor RNA Activator Protein (SRAP): A Potential New Prognostic Marker for Estrogen Receptor-Positive/Node-Negative/Younger Breast Cancer Patients.

Abstract

Purpose: The steroid receptor RNA activator (SRA) is a functional RNA suspected to participate in the mechanisms underlying breast tumor progression. This RNA is also able to encode for a protein, SRAP, whose exact function remains to be determined. Our aim was to assess, in a large breast cancer cohort, whether levels of this protein could be associated with outcome or established clinical parameters.Experimental Design: Following antibody validation, we have assessed SRAP expression by tissue-microarray (TMA) analysis of 372 tumors with known steroid receptor and node status. Clinical follow-up was available for all the corresponding patients. Immunohistochemical scores were independently determined by two investigators and averaged. Statistical analyses were performed using standard univariate and multivariate tests.Results: SRAP levels were significantly (Mann-Whitney rank sum test, P<0.05) higher in estrogen receptor-alpha positive (ER+, n = 273), in progesterone receptor positive (PR+, n= 256) and in older patients (age ≥ 65 years, n = 183). When considering ER+ tumors, PR+ tumors, or young patients (< 65 years), patients with high SRAP expression had a significantly (Mantel-Cox test, P < 0.05) worse breast cancer specific survival (BCSS) than patients with low SRAP levels. SRAP also appeared as a very powerful indicator of poor prognostic for BCSS in the subset of ER+, node negative and young breast cancer patients (Cox regression analysis, n = 60, BCSS Hazard Ratio=13.937, P<0.0001).Conclusion: Our data suggest that SRAP might be a new predictor of breast cancer specific survival in younger breast cancer patients with ER+/node negative tumors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2017.

Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1

“…Western Blot and immunofluorescent microscopy: Western Blot and Immunofluorescent Microscopy were performed as previously described (7). …”

The steroid receptor RNA activator protein (SRAP) controls cancer cell migration/motility

“…Total cell lysates were separated on 10% SDS-PAGE and analyzed by Western blotting as described previously [23].…”

“…As its RNA counterpart, SRAP physically interacts in vitro with several transcription factors [5,21] and might co-activate or repress their action depending on the promoter and the cellular context considered [5,21,22]. We have previously observed that in specific breast cancer subgroups, high levels of SRAP were associated with poor patients survival [23,24]. This suggests that SRAP could be a potential prognostic marker and/or contribute to increasing tumor aggressiveness.…”

Long Noncoding RNAs

“…It is noted to be upregulated in tumors compared with normal tissues, such as breast cancer (Murphy et al 2000 ) and ovarian cancer (Hussein-Fikret and Fuller 2005 ). By tissue-microarray analysis of 372 breast tumors, SRAP levels signifi cantly correlated with ER+, PR+, and older (age >64 years) patients, and higher SRAP expression in ER+, PR+, or younger (age ≤64 years) patients correlated with a worse survival rate (Yan et al 2009 ). By tissue-microarray analysis of 372 breast tumors, SRAP levels signifi cantly correlated with ER+, PR+, and older (age >64 years) patients, and higher SRAP expression in ER+, PR+, or younger (age ≤64 years) patients correlated with a worse survival rate (Yan et al 2009 ).…”