Abstract |
Two proprotein convertase cDNAs, PC1 and furin, were stably transfected into the human breast cancer cell line MCF-7. The PC1 or furin over-expressing cells possessed an altered morphology. When grown in vitro in a serum-free medium, the population doubling time of the convertase-transfected cells was twice that of wild-type (WT) cells. High concentrations of estradiol stimulated the growth of all three cell types to a similar extent; however, at low concentrations of estradiol, the convertase-transfected cells grew more slowly than WT cells. In athymic nude mice implanted with 5 mg estradiol pellets, the growth of tumors of convertase-transfected MCF-7 cells was stimulated to a degree similar to that of WT MCF-7 tumors. However, in mice implanted with lower-dose (1.5 mg) estradiol pellets, the tumors of PC1- or furin-transfected MCF-7 cells grew approximately five times slower than those of WT MCF-7 cells. In mice implanted with tamoxifen pellets, tumors of PC1- or furin-transfected MCF-7 cells regressed approximately five times slower than the WT tumors. This study shows that the over-expression of proprotein convertases confers a greater estrogen dependency and anti- estrogen resistance on human breast cancer cells.
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Authors | M Cheng, N Xu, B Iwasiow, N Seidah, M Chrétien, R P Shiu |
Journal | Journal of molecular endocrinology
(J Mol Endocrinol)
Vol. 26
Issue 2
Pg. 95-105
(Apr 2001)
ISSN: 0952-5041 [Print] England |
PMID | 11241161
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antineoplastic Agents, Hormonal
- Culture Media, Serum-Free
- DNA, Complementary
- Enzyme Precursors
- Receptors, Estrogen
- Tamoxifen
- Estradiol
- Proprotein Convertases
- Subtilisins
- Furin
- Pcsk1 protein, mouse
- Proprotein Convertase 1
- Aspartic Acid Endopeptidases
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Topics |
- Animals
- Antineoplastic Agents, Hormonal
(pharmacology)
- Aspartic Acid Endopeptidases
(genetics, metabolism)
- Blotting, Northern
- Blotting, Southern
- Breast Neoplasms
(pathology)
- Cell Division
(drug effects)
- Cell Size
- Culture Media, Serum-Free
- DNA, Complementary
(genetics, metabolism)
- Enzyme Precursors
(genetics, metabolism)
- Estradiol
(pharmacology)
- Female
- Furin
- Humans
- Immunoblotting
- Mice
- Mice, Nude
- Proprotein Convertase 1
- Proprotein Convertases
- Receptors, Estrogen
(metabolism)
- Subtilisins
(genetics, metabolism)
- Tamoxifen
(pharmacology)
- Transfection
- Transplants
- Tumor Cells, Cultured
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