Keane M M, Lowrey G A, Ettenberg S A, Dayton M A, Lipkowitz S
National Cancer Institute, Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, Maryland 20889-5105, USA.
Cancer Res. 1996 Sep 15;56(18):4236-43.
Sodium butyrate-induced differentiation of breast cancer cell lines was used to identify protein tyrosine phosphatases (PTPs) involved in differentiation and growth inhibition of breast cancer cells. Of 42 PTPs analyzed, 31 were expressed in the ZR75-1 breast cancer cell line. Expression of four PTPs (DEP-1, SAP, PTP gamma, and PAC) was regulated in ZR75-1 cells undergoing differentiation. Expression of two of these PTPs (DEP-1 and SAP) was also regulated in the SKBr-3 cell line undergoing differentiation. In view of its marked induction with differentiation in an estrogen receptor (ER)-positive and an ER-negative breast cancer cell line, DEP-1 was investigated for a role in growth inhibition or induction of differentiation in breast cancer cells. A DEP-1 cDNA construct under control of a constitutively active cytomegalovirus promoter was transfected into the ZR75-1, SKBR-3, and MCF-7 breast cancer cell lines, and resistant colonies were selected with G418. DEP-1 expression inhibited the development of resistant colonies by 3-5-fold in all three lines compared to transfection with vector alone. Three stable MCF-7 cell lines expressing DEP-1 under control of an inducible metallothionein promoter were then established. In these lines, induction of DEP-1 expression inhibited breast cancer cell growth by 5-10-fold. These data describe PTPs expressed and regulated in breast cancer cell lines during differentiation and identify one PTP, DEP-1, that inhibits the growth of breast cancer cells in vitro.
丁酸钠诱导乳腺癌细胞系分化，用于鉴定参与乳腺癌细胞分化和生长抑制的蛋白酪氨酸磷酸酶（PTP）。在分析的42种PTP中，31种在ZR75-1乳腺癌细胞系中表达。四种PTP（DEP-1、SAP、PTPγ和PAC）的表达在ZR75-1分化细胞中受到调控。其中两种PTP（DEP-1和SAP）的表达在SKBr-3分化细胞系中也受到调控。鉴于DEP-1在雌激素受体（ER）阳性和ER阴性乳腺癌细胞系中随分化显著诱导，研究了DEP-1在乳腺癌细胞生长抑制或分化诱导中的作用。将一个受组成型活性巨细胞病毒启动子控制的DEP-1 cDNA构建体转染到ZR75-1、SKBR-3和MCF-7乳腺癌细胞系中，并用G418筛选抗性菌落。与单独转染载体相比，DEP-1表达在所有三个细胞系中使抗性菌落的形成减少了3至5倍。然后建立了三个在可诱导金属硫蛋白启动子控制下表达DEP-1的稳定MCF-7细胞系。在这些细胞系中，DEP-1表达的诱导使乳腺癌细胞生长减少了5至10倍。这些数据描述了分化过程中乳腺癌细胞系中表达和调控的PTP，并鉴定出一种在体外抑制乳腺癌细胞生长的PTP，即DEP-1。
