Data from Ras Signaling Is a Key Determinant for Metastatic Dissemination and Poor Survival of Luminal Breast Cancer Patients

• DOI: 10.1158/0008-5472.c.6508152
• Publication Date: 2023-04-01T01:45:18Z
• Authors: Katherine L. Wright; Jessica R. Adams; Jeff C. Liu; Amanda J. Loch; Ruth G. Wong; Christine E.B. Jo; Lauren A. Beck; Divya R. Santhanam; Laura Weiss; Xue Mei; Timothy F. Lane; Sergei B. Koralov; Susan J. Done; James R. Woodgett; Eldad Zacksenhaus; Pingzhao Hu; Sean E. Egan

<div>Abstract<p>Breast cancer is associated with alterations in a number of growth factor and hormone-regulated signaling pathways. Mouse models metastatic breast typically feature mutated oncoproteins that activate PI3K, Stat3, Ras signaling, but the individual combined roles these pathways progression are poorly understood. In this study, we examined relationship between oncogenic pathway activation subtype by analyzing mouse mammary tumor formation which each was activated singly or pairwise. All three oncogenes showed cooperation during primary formation, efficient dissemination only dependent on Ras. addition, transcriptional profiling demonstrated induced adenocarcinomas molecular characteristics related to human basal-like HER2<sup>+</sup> tumors. contrast, <i>PIK3CA</i><sup><i>H1047R</i></sup>, an mutant linked ERα<sup>+</sup>/luminal humans, luminal B-like Consistent data, elevated tumors humans statistically significant negative association estrogen receptor (ER) across all cancer. Despite this, there signaling. Importantly, when considered as continuous variable, strongly reduced survival patients ERα<sup>+</sup> disease independent PI3K Stat3 activation. Therefore, our studies suggest key determinant for poor prognosis hormone therapy supplemented Ras-targeting agents may be beneficial treating aggressive subtype. <i>Cancer Res; 75(22); 4960–72. ©2015 AACR</i>.</p></div>