Apoptosis of estrogen-receptor negative breast cancer and colon cancer cell lines by PTP alpha and src RNAi.
We show that siRNA-mediated suppression of protein tyrosine phosphatase alpha (PTP alpha) reduces Src activity 2 to 4-fold in breast, colon and other human cancer cell lines. Src and PTP alpha RNAi induced apoptosis in estrogen receptor (ER)-negative breast cancer and colon cancer cells, but not in immortalized noncancerous breast cells, ER-positive breast cancer cells or other cancer cell types tested. RNAi of other Src family members (Fyn and Yes) or of PTP1B, a phosphatase previously suggested to be an activator of Src in breast cancer, had no effect. Although further tests with primary tumor tissues are required, the unexpected correlation between ER status and Src/PTP alpha dependence in breast cancer cell lines may be important for planning therapeutic strategies, and the insensitivity of normal breast cells to the RNAi highlights the potential of PTP alpha, which may be easier to target than Src, as a therapeutic target in ER-negative breast cancer.
Zheng
Xinmin
X
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Resnick
Ross J
RJ
Shalloway
David
D
D017209:Apoptosis; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D024161:Collagen Type XI / Q000378:metabolism; D003110:Colonic Neoplasms / Q000737:chemistry / Q000473:pathology*; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016391:Genes, src; D006801:Humans; D008297:Male; D034741:RNA, Small Interfering / Q000378:metabolism; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000032:analysis*; D019061:src-Family Kinases / Q000235:genetics*
C499319:COL11A2 protein, human; D024161:Collagen Type XI; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D019061:src-Family Kinases; C516841:PTPRA protein, human; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D020169:Caspases