Localization of Mullerian inhibiting substance receptors in various human cancer cell lines.
Recombinant human MIS (rhMIS) produced in transfected Chinese hamster ovary cells has been purified by immunoaffinity chromatography. In the absence of reducing agents, 140 kD homodimer and several oligomers with molecular masses from 280 to 1000 kD are present. Homodimer, tetramer, and higher-molecular-weight rhMIS fractions reduced survival of tumor cells. For these experiments, FITC-labeled rhMIS was used for binding and endocytosis studies by flow cytometry. Flow cytometry performed on MIS-sensitive cancer cell lines demonstrated specific binding of rhMIS. The majority of rhMIS receptors have cytosolic localization. Thus, the level of MIS receptors on the cell membrane was proportional to the content of MIS-binding proteins in the whole cell and defines a level of receptor-mediated endocytosis. The immunopurified rhMIS caused significant growth inhibition of ovarian and prostate adenocarcinoma and melanoma human cell lines in inhibition assays.
Rodina
A V
AV
Moscow Research Institute of Medical Ecology, Moscow Department of Health Care, Moscow, 117638, Russia. allrodina@yandex.ru.
Gukasova
N V
NV
Makarov
V A
VA
Kondrasheva
I G
IG
Khomyakova
A V
AV
Posypanova
G A
GA
Popova
O N
ON
Moskaleva
E Yu
EY
Severin
S E
SE
D000818:Animals; D054304:Anti-Mullerian Hormone / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016466:CHO Cells; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis; D006801:Humans; D018000:Receptors, Peptide / Q000032:analysis* / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis* / Q000378:metabolism; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology
D000970:Antineoplastic Agents; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone