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Tytuł oryginału: Differential expression of the mannose 6-phosphate/insulin-like growth factor-II receptor in human breast cancer cell lines of different invasive potential.
Autorzy: Xie Suqing, Kang Jing X.
Źródło: Med. Sci. Monitor 2002: 8 (8) s.BR293-BR300, il., bibliogr. 28 poz.
Sygnatura GBL: 313,278

Hasła klasyfikacyjne GBL:
  • onkologia

    Typ dokumentu:
  • praca doświadczalna
  • tytuł obcojęzyczny

    Wskaźnik treści:
  • ludzie
  • in vitro

    Streszczenie angielskie: Hypersecretion of the precursor of the lysosomal protease cathepsin D (procatherpsin D) has been implicated in the invasive phenotype of human breast cancer. However, the mechanism of the abnormal secretion of procathepsin D remains unclear. Since the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) plays a central role in the intracellular transport and endocytosis of M6P-containing lysosomal enzymes, a deficiency in functional M6P/IGF2R may underline the hypersecretion of procathepsin D in invasive tumors. Materal/Methds: In the present study, we compared the profiles of cathepsin D and the M6P/IGF2R between the highly invasive MDA-MB-231 and the non-invasive MCF-7 cell lines. Results: MDA-MB-231 cells were confirmed to secrete a much larger proportion of procathepsin D into the medium than MCF-7 cells. Addition of M6P to the culture medium significantly altered the secretion of procathepsin D by MCF-7 cells, but had little effect on cathepsin D distribution in MDA-MB-23 cells. Both the M6P-binding capacity and the endocytosis of exogenous M6P-bearing proteins in MDA-MB-231 cells were far less than those in MCF-7 cells. mRNA analysis indicated that the levels of the M6P/IGF2R mRNA in MDA-MB-231 cells were not lower but were even higher than that in MCF-7 cells. Sequence analysis indicated a difference in the 3'-untranslated region of M6P/IGF2R between the two cell lines, but no mutation in the M6P-binding domain of the receptor. Conclusions: The results suggest that a potential defect in a post-transcriptional process (e.g., translation) may exist during synthesis of the m6P/IGF2R n MDA-MB-231 cells, leading to failure to express sufficient functional M6P/IGF2R and thereby resulting in the hypersecretion of procathepsin D...

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