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Pieretti-Vanmarcke R , Donahoe PK , Pearsall LA , Dinulescu DM , Connolly DC , Halpern EF , Seiden MV , MacLaughlin DT
Mullerian inhibiting substance enhances subclinical doses of chemotherapeutic agents to inhibit human and mouse ovarian cancer
Proceedings of the National Academy of Sciences of the United States of America. 2006 Nov;103(46) :17426-17431
PMID: ISI:000242249400065   
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Abstract
Mullerian Inhibiting Substance (MIS), a biological modifier that causes regression of Mullerian ducts in male embryos, is effective as a single agent in vitro and in vivo against human and mouse ovarian cancer cell lines expressing MIS type 11 receptor; however, little is known about how recombinant human MIS (rhMIS), now being scaled for preclinical trials, could be used in combination with cytotoxic or targeted chemotherapeutic agents. Mouse serous and endometrioid ovarian carcinoma cell lines were tested in vitro against rhMIS alone and with doxorubicin, paclitaxel, or cisplatin as agents in clinical use. Because MIS releases FK506 binding protein (FKBP12), which activates the mammalian target of rapamycin (mTOR) downstream of Akt, rhMIS and rapamycin combinations were tested. MIS increases p16 protein levels, and 5'-Aza2'-deoxycytidine (AzadC) induces p16 mRNA; therefore, they were used in combination in vitro and in vivo with a human ovarian cancer cell line. A paclitaxel-resistant human ovariain cancer cell line and its parental line both respond to rhMIS in vitro. Additivity, synergy, or competition was observed with MIS and rapamycin, AzadC, doxorubicin, cisplatin, and paclitaxel, suggesting that MIS in combination with selective targeted therapies might achieve greater activity against ovarian cancer than the use of each individual agent alone. These assays and statistical analyses could be useful in selecting rhMIS and chemotherapeutic agent combinations that enhance clinical efficacy and reduce toxicity.
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ISI Document Delivery No.: 108OP Times Cited: 0 Cited Reference Count: 63 Cited References: BAARENDS WM, 1994, DEVELOPMENT, V120, P189 BARBIE TU, 2003, P NATL ACAD SCI USA, V100, P15601 BASELGA J, 1998, CANCER RES, V58, P2825 BENARD J, 1985, CANCER RES, V45, P4970 BUSTIN SA, 1994, BRIT J BIOMED SCI, V51, P147 CATE RL, 1986, CELL, V45, P685 CHIN TW, 1991, CANCER RES, V51, P2101 CLARKE TR, 2001, MOL ENDOCRINOL, V15, P946 CONNOLLY DC, 2003, CANCER RES, V63, P1389 DICLEMENTE N, 1994, MOL ENDOCRINOL, V8, P1006 DINULESCU DM, 2005, NAT MED, V11, P63 DONAHOE PK, 1977, J SURG RES, V23, P141 DONAHOE PK, 1979, SCIENCE, V205, P913 GERA JF, 2004, J BIOL CHEM, V279, P2737 GONZALEZ S, 2006, NATURE, V440, P702 GORDON AN, 2004, GYNECOL ONCOL, V95, P1 GOUEDARD L, 2000, J BIOL CHEM, V275, P27973 GU ZY, 1999, DEVELOPMENT, V126, P2551 GUSTAFSON ML, 1992, NEW ENGL J MED, V326, P466 HA TU, 2000, J BIOL CHEM, V275, P37101 HAINSWORTH JD, 2005, J CLIN ONCOL, V23, P7889 HAYASHI A, 1982, DEV BIOL, V92, P16 HERMAN JG, 1995, CANCER RES, V55, P4525 HOSHIYA Y, 2003, J BIOL CHEM, V278, P51703 HOSHIYA Y, 2003, MOL CELL ENDOCRINOL, V211, P43 HURWITZ H, 2004, NEW ENGL J MED, V350, P2335 ISSA JPJ, 2005, J CLIN ONCOL, V23, P3948 JAMIN SP, 2002, NAT GENET, V32, P408 JEMAL A, 2003, CA-CANCER J CLIN, V53, P5 JOHNSON SW, 1997, CANCER RES, V57, P850 LANE AH, 1999, GYNECOL ONCOL, V73, P51 LEE MM, 1997, NEW ENGL J MED, V336, P1480 LORENZO HK, 2002, J CHROMATOGR B, V766, P89 MASIAKOS PT, 1999, CLIN CANCER RES, V5, P3488 MERIO A, 1995, NAT MED, V1, P686 OTTERSON GA, 1995, ONCOGENE, V11, P1211 PARRY RL, 1992, CANCER RES, V52, P1182 PIERETTIVANMARCKE R, 2006, CLIN CANCER RES, V12, P1593 PRICE JM, 1977, AM J ANAT, V149, P353 PRICE JM, 1979, AM J ANAT, V156, P265 RAGIN RC, 1992, PROTEIN EXPRES PURIF, V3, P236 RENAUD EJ, 2005, P NATL ACAD SCI USA, V102, P111 REYA T, 2001, NATURE, V414, P105 SCHEFFE H, 1959, ANAL VARIANCE, P90 SEGEV DL, 2000, J BIOL CHEM, V275, P28371 SEGEV DL, 2001, J BIOL CHEM, V276, P26799 SEGEV DL, 2002, P NATL ACAD SCI USA, V99, P239 SLAMON DJ, 2001, NEW ENGL J MED, V344, P783 STEINIGER SCJ, 2004, INT J CANCER, V109, P759 STEPHEN AE, 2001, P NATL ACAD SCI USA, V98, P3214 STEPHEN AE, 2002, CLIN CANCER RES, V8, P2640 SZOTEK PP, 2006, P NATL ACAD SCI USA, V103, P11154 TEIXEIRA J, 1996, ENDOCRINOLOGY, V137, P160 TEIXEIRA J, 1999, ENDOCRINOLOGY, V140, P4732 TEIXEIRA J, 1999, P NATL ACAD SCI USA, V96, P13831 TRBOVICH AM, 2001, P NATL ACAD SCI USA, V98, P3393 TRELSTAD RL, 1982, DEV BIOL, V92, P27 VISSER JA, 2001, MOL ENDOCRINOL, V15, P936 WANG PY, 2005, P NATL ACAD SCI USA, V102, P16421 WANG TW, 1996, CELL, V86, P435 WANG TW, 2004, FRONT BIOSCI, V9, P619 ZHAN Y, 2006, DEVELOPMENT, V133, P2359 ZHOU XY, 2004, CLIN CANCER RES, V10, P6779