Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-2-27
pubmed:abstractText
The human insulin analogue ASPB10 has been reported to have increased affinity for the insulin receptor and to cause breast cancer in female rats. In the study reported here, we investigated whether ASPB10 has an increased mitogenic potency and induces a transformed phenotype in cultured human breast cells. In both MCF-10 cells (a non-malignant human breast line) and MCF-7 cells (a human breast cancer cell line), ASPB10 was approximately twofold more potent than insulin in competing for 125I-insulin binding but sevenfold to tenfold more potent than insulin in competing for 125I-insulin-like growth factor (IGF)-I binding. In addition, ASPB10 was twofold more potent than insulin in stimulating insulin receptor autophosphorylation but significantly more potent in stimulating IGF-I receptor autophosphorylation in both cell lines. Moreover, ASPB10 was approximately sevenfold more potent than insulin in stimulating the growth of MCF-10 and MCF-7 cells. This increased mitogenic effect of ASPB10 was significantly inhibited (but not abolished) when cells were cultured in the presence of alpha-IR3, a monoclonal antibody to the IGF-I receptor. ASPB10, but not insulin, caused phenotypic changes (focus formation) in MCF-10 cells. Neither agent caused colony formation in soft agar in MCF-10 cells, but ASPB10 was more potent than insulin in stimulating colony formation in MCF-7 cells. These observations indicate that in human breast cells, ASPB10 has enhanced mitogenic effects and induces phenotypic changes as a consequence of its activation of both insulin and IGF-I receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0899-1987
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19-25
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
ASPB10 insulin induction of increased mitogenic responses and phenotypic changes in human breast epithelial cells: evidence for enhanced interactions with the insulin-like growth factor-I receptor.
pubmed:affiliation
Cattedra di Endocrinologia dell'Università di Catania, Ospedale Garibaldi, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't