Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
PLoS One. 2012;7(3):e33017. doi: 10.1371/journal.pone.0033017. Epub 2012 Mar 22.
Src, a non-receptor tyrosine kinase is elevated in cancer with expression and activity correlated with cell proliferation, adhesion, survival, motility, metastasis and angiogenesis. There is limited data on Src expression and subcellular localization in breast cancer and no information about expression in racial/ethnic groups.
METHODOLOGY/PRINCIPAL FINDINGS: The present study evaluated Src expression, activity, and subcellular localization in triple negative breast cancer (TNBC) and ERα positive breast cancer (ER+BC), cancer tissue and adjacent normal epithelial ducts, and Caucasian and African American cases. 79 paraffin embedded breast carcinoma cases were obtained from Tulane University Hospital between 2007-2009. 39 cases represented TNBC (33-African Americans, 4-Caucasians, 2-unknowns) and 40 cases represented ER+BC (21-African Americans, 16-Caucasians, 3-unknowns). Immunohistochemistry was used to measure staining distribution and intensity of total Src and activated phospho-SrcY416 (p-Y416Src) in carcinoma tissue and adjacent normal mammary ducts. In TNBC and ER+BC, total Src was significantly higher in cancer compared to adjacent normal ducts (P<0.0001) in both cell membrane and cytoplasm. In membranes, p-Y416Src was elevated in cancer compared to normal ducts. Total Src in the tumor cytoplasm was significantly higher in TNBC compared to ER+BC (P = 0.0028); conversely, p-Y416Src in the tumor cell membranes was higher in TNBC compared to ER+BC (P = 0.0106). Comparison between African American (n = 21) and Caucasian ER+BC (n = 16) revealed no significant difference in expression and localization of total Src and p-Y416Src. TNBC cases positive for lymph node metastasis showed elevated membrane p-Y416Src compared to lymph node negative TNBC (P = 0.027).
CONCLUSION/SIGNIFICANCE: Total Src and p-Y416Src were expressed higher in cancer compared to adjacent normal ducts. Cytoplasmic total Src and membrane p-Y416Src were significantly higher in TNBC compared to ER+BC. TNBC cases with lymph node metastasis showed elevated membrane p-Y416Src. Taken together, Src was elevated in the membrane and cytoplasm of more aggressive TNBC.
Src 是非受体酪氨酸激酶，在癌症中表达升高，其表达和活性与细胞增殖、黏附、存活、运动、转移和血管生成有关。关于 Src 在乳腺癌中的表达和亚细胞定位的数据有限，并且没有关于其在不同种族/民族群体中表达的信息。
方法/主要发现：本研究评估了三阴性乳腺癌（TNBC）和 ERα 阳性乳腺癌（ER+BC）、癌组织和相邻正常上皮导管以及白种人和非裔美国人病例中 Src 的表达、活性和亚细胞定位。从 2007 年至 2009 年，从杜兰大学医院获得了 79 例石蜡包埋的乳腺癌病例。39 例代表 TNBC（33 例为非裔美国人，4 例为白种人，2 例未知），40 例代表 ER+BC（21 例为非裔美国人，16 例为白种人，3 例未知）。免疫组织化学用于测量癌组织和相邻正常乳腺导管中总 Src 和激活的磷酸化 SrcY416（p-Y416Src）的染色分布和强度。在 TNBC 和 ER+BC 中，与相邻正常导管相比，癌组织中总 Src 在细胞膜和细胞质中均显著升高（P<0.0001）。在膜中，p-Y416Src 在癌症中比正常导管中升高。与 ER+BC 相比，TNBC 肿瘤细胞质中的总 Src 显著升高（P=0.0028）；相反，TNBC 肿瘤细胞膜中的 p-Y416Src 高于 ER+BC（P=0.0106）。比较非裔美国人（n=21）和白种人 ER+BC（n=16）发现，总 Src 和 p-Y416Src 的表达和定位没有差异。与淋巴结阴性 TNBC 相比，淋巴结转移阳性的 TNBC 显示膜 p-Y416Src 升高（P=0.027）。
结论/意义：与相邻正常导管相比，癌组织中总 Src 和 p-Y416Src 的表达更高。与 ER+BC 相比，TNBC 中细胞质中的总 Src 和膜中的 p-Y416Src 显著升高。淋巴结转移的 TNBC 病例显示膜 p-Y416Src 升高。总之，Src 在更具侵袭性的 TNBC 的膜和细胞质中升高。
