Mad2beta, an alternative variant of Mad2 reducing mitotic arrest and apoptosis induced by adriamycin in gastric cancer cells.
Mad2beta is an alternative splicing variant of spindle checkpoint gene mad2, which was previously found by us and was related to the drug resistance in gastric cancer cells. In this paper, we explored the molecular mechanisms that Mad2beta variant promoted the formation of multidrug resistance in gastric cancer cells. We found that Mad2beta variant was detected only in the two human drug resistant gastric cancer cell sublines SGC7901/VCR and SGC7901/ADR, and it did not appear in its parental cell line SGC7901 and other detected gastric cancer cell lines. Expressions of Mad2 mRNA and protein in SGC7901 cells transfected with Mad2beta, SGC7901/VCR and SGC7901/ADR were significantly lower than that in SGC7901 cells. Moreover, SGC7901 cells overexpressing Mad2beta variant became more resistant to adriamycin, vincristine and mitomycin by abrogating mitotic arrest and apoptosis. This suggests that expression of Mad2beta variant decreases the relative expression of efficient MAD2, which may help gastric cancer cells to develop the phenotype of multidrug resistance.
Yin
Fang
F
Department of Gastroenterology, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Du
Yulei
Y
Hu
Wenhua
W
Qiao
Taidong
T
Ding
Jie
J
Wu
Kaichun
K
Liu
Zhiguo
Z
Fan
Daiming
D
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D014644:Genetic Variation; D006801:Humans; D064246:Mad2 Proteins; D008938:Mitosis / Q000187:drug effects*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D014162:Transfection
D000964:Antimetabolites, Antineoplastic; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D004317:Doxorubicin