THE PROTEIN-TYROSINE-PHOSPHATASE DEP-1 IS INDUCED DURING DIFFERENTIATION AND INHIBITS GROWTH OF BREAST-CANCER CELLS

Sodium butyrate-induced differentiation of breast cancer cell lines wa s used to identify protein tyrosine phosphatases (PTPs) involved in di fferentiation and growth inhibition of breast cancer cells. Of 42 PTPs analyzed, 31 were expressed in the ZR75-1 breast cancer cell line, Ex pression of four PTPs (DEP-1, SAP, PTP gamma, and PAC) was regulated i n ZR75-1 cells undergoing differentiation. Expression of two of these PTPs (DEP-1 and SAP) was also regulated in the SKBr-3 cell line underg oing differentiation. In view of its marked induction sith differentia tion in an estrogen receptor (ER)-positive and an ER-negative breast c ancer cell line, DEP-1 was investigated for a role in growth inhibitio n or induction of differentiation in breast cancer cells. A DEP-1 cDNA construct under control of a constitutively active cytomegalovirus pr omoter was transfected into the ZR75-1, SKBR-3, and MCF-7 breast cance r cell lines, and resistant colonies were selected with G418, DEP-1 ex pression inhibited the development of resistant colonies by 3-5-fold i n all three lines compared to transfection with vector alone, Three st able MCF-7 cell lines expressing DEP-1 under control of an inducible m etallothionein promoter mere then established, In these lines, inducti on of DEP-1 expression inhibited breast cancer cell growth by 5-10-fol d. These data describe PTPs expressed and regulated in breast cancer c ell lines during: differentiation and identify one PTP, DEP-1, that in hibits the growth of breast cancer cells in vitro.