Mullerian Inhibiting Substance induces NFkB signaling in breast and prostate cancer cells.
The MIS type II receptor is expressed at high levels in the Mullerian duct and in Sertoli cells and granulosa cells of the embryonic and adult gonads. The presence of MIS type II and type I receptors in tissues and cell lines derived from breast and prostate suggests that the prostate and mammary glands may be additional targets for MIS action. In both breast and prostate cancer cells, MIS activated NFkB DNA binding activity and induced IEX-1, an immediate early gene which regulates cell growth and apoptosis. Exposure of cells to MIS inhibited growth by increasing the fraction of cells in the G1 phase of the cell cycle and by inducing apoptosis. These results suggest that MIS may be a putative mediator of growth regulatory signals in the breast and prostate.
Hoshiya
Yasunori
Y
Pediatric Surgical Research Laboratories, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Gupta
Vandana
V
Segev
Dorry L
DL
Hoshiya
Makiko
M
Carey
Jennifer L
JL
Sasur
Laura M
LM
Tran
Trinh T
TT
Ha
Thanh U
TU
Maheswaran
Shyamala
S
D030201:Activin Receptors, Type I / Q000235:genetics; D000818:Animals; D054304:Anti-Mullerian Hormone; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D052005:Bone Morphogenetic Protein Receptors, Type I; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009363:Neoplasm Proteins / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013735:Testicular Hormones / Q000494:pharmacology*; D051996:Transcription Factor RelA
D051017:Apoptosis Regulatory Proteins; D006023:Glycoproteins; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009363:Neoplasm Proteins; D017978:Receptors, Growth Factor; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D013735:Testicular Hormones; D051996:Transcription Factor RelA; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D052005:Bone Morphogenetic Protein Receptors, Type I