title: Subcellular localization of total and activated Src kinase in African American and Caucasian breast cancer.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Muralidharan
authors.initials: M
authors.lastname: Anbalagan
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Moroz
authors.forename: Alaa
authors.initials: A
authors.lastname: Ali
authors.forename: Latonya
authors.initials: L
authors.lastname: Carrier
authors.forename: Seth
authors.initials: S
authors.lastname: Glodowski
authors.forename: Brian G
authors.initials: BG
authors.lastname: Rowan
mesh_terms: D044383:Black People; D001943:Breast Neoplasms / Q000201:enzymology* / Q000208:ethnology / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D016612:Paraffin Embedding; D011960:Receptors, Estrogen / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology*; D044465:White People; D019061:src-Family Kinases / Q000378:metabolism*; D001741:Black or African American
chemical_list: D011960:Receptors, Estrogen; D019061:src-Family Kinases