Breast cancer patients’ clinical outcome measures are associated with Src kinase family member expression

Abstract

Background:This study determined mRNA expression levels for Src kinase family (SFK) members in breast tissue specimens and assessed protein expression levels of prominent SFK members in invasive breast cancer to establish associations with clinical outcome. Ki67 was investigated to determine association between SFK members and proliferation.Methods:The mRNA expression levels were assessed for eight SFK members by quantitative real-time PCR. Immunohistochemistry was performed for c-Src, Lyn, Lck and Ki67.Results:mRNA expression was quantified in all tissue samples. SRC and LYN were the most highly expressed in malignant tissue. LCK was more highly expressed in oestrogen receptor (ER)-negative, compared with ER-positive tumours. High cytoplasmic Src kinase protein expression was significantly associated with decreased disease-specific survival. Lyn was not associated with survival at any cellular location. High membrane Lck expression was significantly associated with improved survival. Ki67 expression correlated with tumour grade and nuclear c-Src, but was not associated with survival.Conclusions:All eight SFK members were expressed in different breast tissues. Src kinase was highest expressed in breast cancer and had a negative impact on disease-specific survival. Membrane expression of Lck was associated with improved clinical outcome. High expression of Src kinase correlated with high proliferation.

Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant

“…Importantly, despite clear differences between cell culture conditions and the 3D microenvironment in intact tumor tissue, a systematic analysis of in vitro screening data, with a clear clinical cancer progression end point and in vivo testing, constitutes a powerful experimental pipeline for identifying novel, likely drug-target candidates. (40). This is in agreement with our data, which also show that patients with high LCK levels have favorable MFS compared with patients with low levels of this kinase ( Figure 3A).…”

Actin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells

“…Src protein levels and, to a greater extent, Src protein kinase activity are frequently elevated in malignant and non-malignant breast tissues and significantly associated with decreased survival of breast cancer patients45.…”

Dasatinib plus Capecitabine for Advanced Breast Cancer: Safety and Efficacy in Phase I Study CA180004

“…Elevated expression or activity of Src kinase in breast cancer has been associated with metastasis to bone (8,9) with tumor cell invasiveness (10) and with poorer clinical outcomes (11). Src activity has been shown to mediate signaling by growth factor receptors including EGF receptor (EGFR; ref.…”