The human myoepithelial cell exerts antiproliferative effects on breast carcinoma cells characterized by p21WAF1/CIP1 induction, G2/M arrest, and apoptosis.
Ductal carcinoma in situ of the breast (DCIS) is surrounded by a layer of myoepithelial cells. Our previous studies have suggested that these myoepithelial cells exert paracrine tumor-suppressive effects on invasion of breast carcinoma cells. Conditioned medium (CM), concentrated 10-100x of HMS-1, HMS-3, and HMS-4, human myoepithelial cell lines, block Matrigel invasion of a series of carcinoma cell lines. Immunoprecipitation of maspin, a recently described serpin, from these CM abolishes this anti-invasive effect. Both CM and maspin-immunoprecipitated CM, however, exert equal antiproliferative effects on a series of ER+ and ER- cell lines including MCF-7, T47D, MDA-MB-231, and MDA-MB-468. These antiproliferative effects are characterized by induction of a G2/M arrest, a twofold increase in p21(WAF1/CIP1) transcription and expression, and a threefold increase in apoptosis in the breast carcinoma lines examined. The antiproliferative effects mediated by myoepithelial cell CM do not manifest themselves in an autocrine manner, are not mediated by TGF-beta1, nor involve ER- or p53-dependent pathways. Neither the antiproliferative nor the anti-invasive effects of myoepithelial cell CM is observed with nonmyoepithelial cell CM. The in vitro observations of our present study may have relevance in explaining the increased degree of apoptosis exhibited by DCIS cells in vivo. Our findings illustrate another way myoepithelial cells function as natural paracrine tumor suppressors.
Shao
Z M
ZM
Department of Pathology, UCLA School of Medicine, Los Angeles, California, 90024, USA.
Nguyen
M
M
Alpaugh
M L
ML
O'Connell
J T
JT
Barsky
S H
SH
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology; D002277:Carcinoma / Q000473:pathology* / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; D017077:Culture Media, Conditioned; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins