Structural and functional studies of insulin receptors in human breast cancer

Structural and functional studies of insulin receptors in human breast cancer (119 visite)

FRITTITTA L, VIGNERI R, PAPA V, GOLDFINE I, GRASSO G, TRISCHITTA V

Breast Cancer Res Tr Kluwer Academic Publishers (ISSN: 0167-6806), 1993; 25(1): 73-82.

Tipo di articolo: Journal Article,

Impact factor: 2.43, Impact factor a 5 anni: 4.024

Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-0027409865&partnerID=40&md5=f259967832a3cc6279dcefb46f1d2853

Parole chiave: Growth Factors, Insulin Sensitivity, Oncogenes, Receptor Growth Factors, Tyrosine Kinase, Adenosine Triphosphate, Insulin Receptor, Messenger Rna, Protein Tyrosine Kinase, Alpha Chain, Article, Autophosphorylation, Beta Chain, Breast, Breast Cancer, Comparative Study, Controlled Study, Cross Linking, Enzyme Activity, Female, Human, Human Tissue, Immunoprecipitation, Polyacrylamide Gel Electrophoresis, Radioimmunoassay, Receptor Binding, Structure Activity Relation, Breast Neoplasms, Peptide Fragments, Protein-Tyrosine Kinase, Reference Values, Structure-Activity Relationship, Support, Non-U.S. Gov, Non-U. S. Gov,

Affiliazioni:

Cattedra di Endocrinologia e Patologia Costituzionale, Università di Catania, Ospedale Garibaldi, USL 34, Piazza S.M. di Gesù, Catania, 95123, Italy
Diabetes and Endocrine Research, Mount Zion Medical Center, and Department of Medicine and Physiology, University of California San Francisco, San Francisco, 94120, CA, United States

Riferimenti:

Non disponibile.

We characterized the structure and the function of insulin receptors isolated from 10 human breast cancer specimens. We observed that the insulin receptor content, as determined by a specific radioimmunoassay, was four fold increased in human breast cancer tissue when compared to normal breast tissues. In both cancer and normal breast tissues, insulin receptor mRNA consisted of two major species of approximately 11.0 and 8.5 kilobases. The size of the insulin receptor alpha subunit was determined by125I-insulin cross-linking followed by immunoprecipitation and polyacrylamide gel electrophoresis; a value of 135 kDa was observed for receptors from both breast cancer and normal breast tissues. The functional binding ability of insulin receptors from cancer tissues was slightly lower as compared to normal tissue derived insulin receptor (% B/T= 2.22±0.50 per ng of insulin receptor as determined by radioimmunoassay vs. 2.96±0.49, mean±S.E.M.). The concentration of insulin that caused half maximal inhibition of125I-insulin binding was very similar for both cancer and normal breast receptors (80pM). The size of the insulin receptor beta subunit as determined by receptor autophosphorylation was 95kDa. Basal and maximal insulin (100nM) stimulated receptor tyrosine kinase activity, in terms of both receptor autophosphorylation and phosphorylation of an exogenous substrate, was similar in malignant and normal breast tissue derived insulin receptor. Also, a very similar insulin stimulated Km value for ATP was showed by the tyrosine kinase of insulin receptors from breast cancer and normal breast tissue (11.1 and 10.8μM ATP, respectively). However, in insulin receptors from breast cancer tissue the average tyrosine kinase sensitivity to insulin, as calculated on the exogenous substrate, was higher, although not significantly, with respect to normal breast tissue (ED50 at 0.28±0.09 and 1.08±0.33 nM insulin, respectively). A similarly different sensitivity to insulin was observed also for receptor autophosphorylation. In conclusion, this study demonstrates that breast cancer tissues have an increased number of structurally and functionally normal insulin receptors. In some breast cancer tissues, however, the sensitivity of the receptor tyrosine kinase activity to insulin is greatly increased. These data suggest that, in vivo, the mitogenic effect of insulin may play a role in the biology of certain breast cancers. © 1993 Kluwer Academic Publishers.

Interrogazione effettuata: [atitle, keywords] "Growth Factors" OR [atitle, keywords] "Insulin Sensitivity" OR [atitle, keywords] "Oncogenes" OR [atitle, keywords] "Receptor Growth Factors" OR [atitle, keywords] "Tyrosine Kinase" OR [atitle, keywords] "Adenosine Triphosphate" OR [atitle, keywords] "Insulin Receptor"

▼ Monoclonal Antibodies for therapeutic and diagnostic applications

Ruvo Menotti

Interrogazione effettuata: [ptitle] "Growth Factors" OR [ptitle] "Insulin Sensitivity" OR [ptitle] "Oncogenes" OR [ptitle] "Receptor Growth Factors" OR [ptitle] "Tyrosine Kinase" OR [ptitle] "Adenosine Triphosphate" OR [ptitle] "Insulin Receptor"

Nessun risultato.

Interrogazione effettuata: [btitle, keywords] "Growth Factors" [btitle, keywords] "Insulin Sensitivity" [btitle, keywords] "Oncogenes" [btitle, keywords] "Receptor Growth Factors" [btitle, keywords] "Tyrosine Kinase" [btitle, keywords] "Adenosine Triphosphate" [btitle, keywords] "Insulin Receptor"

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Papa V, Reese CC, Brunetti A, Vigneri R, Siiteri PK, Goldfine ID
Progestins increase insulin receptor content and insulin stimulation of growth in human breast carcinoma cells (94 visite)
Cancer Res (ISSN: 0008-5472, 1538-7445, 1538-7445electronic), 1990 Dec 15; 50(24): 7858-7862.
Impact Factor: 8.426
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Trischitta V, Brunetti A, Chiavetta A, Benzi L, Papa V, Vigneri R
Defects in insulin-receptor internalization and processing in monocytes of obese subjects and obese NIDDM patients (99 visite)
Diabetesdiabetes (ISSN: 0012-1797), 1989 Dec; 38(12): 1579-1584.
Impact Factor: 8.675
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Pezzino V, Papa V, Trischitta V, Brunetti A, Goodman PA, Treutelaar MK, Williams JA, Maddux BA, Vigneri R, Goldfine ID
Human insulin receptor radioimmunoassay: Applicability to insulin-resistant states (97 visite)
Am J Physiol Endocrinol Metab (ISSN: 0002-9513), 1989 Sep; 257(3): N/D-N/D.
Impact Factor: 3.116
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Trischitta V, Wong KY, Brunetti A, Scalisi R, Vigneri R, Goldfine ID
Endocytosis, recycling, and degradation of the insulin receptor. Studies with monoclonal antireceptor antibodies that do not activate receptor kinase (99 visite)
J Biol Chem (ISSN: 0021-9258, 1083-351x), 1989 Mar 25; 264(9): 5041-5046.
Impact Factor: 6.963
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Romano M, Cerra M, Salvatore M, Onorati A
Effects of ionizing radiations on the activity of valyl tRNA synthetase isolated from rat liver and from Morris hepatoma 7777 (94 visite)
Tumori (ISSN: 0300-8916, 0300-8916print), 1974 Jul; 60(4): 301-306.
Impact Factor: 0.408
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54 Records (43 escludendo Abstract e Conferenze).
Impact factor totale: 281.44 (237.034 escludendo Abstract e Conferenze).
Impact factor a 5 anni totale: 273.972 (234.902 escludendo Abstract e Conferenze).

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