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Decreased expression of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor in invasive cell clones derived from human prostate and breast tumor cells.

Abstract：

:The importance of receptors involved in the clearance of proteases and protease/inhibitor complexes in tumor invasion is unknown. We studied the expression of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2-MR), the major receptor involved in the clearance of protease/inhibitor complexes, in invasive and noninvasive subclones derived from tumor cells. The receptor activity was 2- to 3-fold lower in invasive subclones compared to noninvasive subclones derived from human prostate PC-3 and DU 145 and melanoma A2058 cells. The receptor activity was decreased in breast cancer (MCF-10A) cells transfected with mutated Ha-ras compared to nontransfected cells. Furthermore, invasive cells derived from ras-transfected MCF-10A cells expressed lower levels of receptor compared to their non-invasive counterparts. These studies indicate a correlation between invasive phenotype and low receptor expression in different tumor cells. Experiments were performed to understand two possible mechanisms (decreased transcription of the receptor and increased transcription of an inhibitory protein) for the decreased cell-surface expression of the receptor in invasive cells. The decreased expression in invasive subclones was due to 2- to 3-fold lower levels of LRP/alpha 2-MR mRNA in all cells. In invasive PC-3 subclones, but not in DU 145, A2058, and MCF-10A subclones, 2-fold higher levels of the 39 kDa receptor-associated protein (an inhibitor of the receptor) mRNA were observed. These studies showed that the decreased expression of LRP/alpha 2-MR activity in invasive subclones was generally correlated with the decreased steady-state mRNA levels of the receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Oncol Res

journal_title

Oncology research

authors

Kancha RK,Stearns ME,Hussain MM

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

365-72

issue

eissn

0965-0407

issn

1555-3906

journal_volume

pub_type

杂志文章

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Decreased expression of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor in invasive cell clones derived from human prostate and breast tumor cells.