Involvement of insulin-like growth factors-I and-II and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas
The role of the insulin-like growth factors (IGFs) system was investigated in hormone-dependent (HD) and -independent (HI) in vivo lines of the medroxyprogesterone acetate (MPA)-induced mammary tumor model in Balb/c mice. IGF-II protein and message showed a three- to four-fold increase in HD lines g...
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1998
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09600760_v67_n4_p305_Elizalde http://hdl.handle.net/20.500.12110/paper_09600760_v67_n4_p305_Elizalde |
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paper:paper_09600760_v67_n4_p305_Elizalde2023-06-08T15:57:26Z Involvement of insulin-like growth factors-I and-II and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas somatomedin b somatomedin b receptor somatomedin c somatomedin c receptor animal cell animal experiment animal model animal tissue article breast adenocarcinoma breast epithelium cancer growth cell proliferation controlled study female in situ hybridization mouse nonhuman protein expression Adenocarcinoma Animals Base Sequence Cell Division Female In Situ Hybridization Insulin-Like Growth Factor I Insulin-Like Growth Factor II Mammary Neoplasms, Experimental Medroxyprogesterone 17-Acetate Mice Mice, Inbred BALB C Oligonucleotides, Antisense Receptor, IGF Type 1 Receptor, IGF Type 2 Tumor Cells, Cultured Animalia The role of the insulin-like growth factors (IGFs) system was investigated in hormone-dependent (HD) and -independent (HI) in vivo lines of the medroxyprogesterone acetate (MPA)-induced mammary tumor model in Balb/c mice. IGF-II protein and message showed a three- to four-fold increase in HD lines growing in MPA-treated mice, as compared with HD tumors growing in untreated mice. Progression to a hormone-independent phenotype in all these lines was accompanied by a high constitutive expression of IGF-II. Similar IGF-I mRNA levels were detected in HD and HI lines. Both IGE-I and -II messages arose from the malignant epithelial cells, as shown by in situ hybridization studies. A significant decrease in Man-6P/type II IGF-R content was detected in HD tumors growing in MPA-treated mice as compared with HD lines growing in untreated mice. On the other hand, in HI tumors, notwithstanding high IGF-II synthesis, the levels of Man-6P/type II IGF-R remain high. Competitive inhibition and affinity labeling studies showed an almost exclusive binding of IGF-II to Man-6P/type II IGF-R on tumor membranes. The involvement of IGFs in the growth of epithelial primary cultures of the C4-HD line was evaluated. Exogenous IGF-I potentiated MPA stimulatory effect at concentrations of 50-100 ng/ml. Treatment of C4-HD cells with antisense oligodeoxynucleotides (ASODNs) to type I IGF-R and to IGF-II RNA resulted in a dose-dependent inhibition of MPA-mediated cell proliferation. The inhibition caused by IGF-II ASODNs could not be overcome by the addition of IGF-II up to 150 ng/ml. ASODNs to type I IGF-R at 40 μg/ml reduced by 75% the number of type I IGF-R; ASODNs to IGF-II at 1 μM decreased by 83% the levels of IGF-II protein. Our results provide support for the involvement of IGE-I and -II in MPA-induced mammary tumor growth by autocrine pathways. 1998 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09600760_v67_n4_p305_Elizalde http://hdl.handle.net/20.500.12110/paper_09600760_v67_n4_p305_Elizalde |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
somatomedin b somatomedin b receptor somatomedin c somatomedin c receptor animal cell animal experiment animal model animal tissue article breast adenocarcinoma breast epithelium cancer growth cell proliferation controlled study female in situ hybridization mouse nonhuman protein expression Adenocarcinoma Animals Base Sequence Cell Division Female In Situ Hybridization Insulin-Like Growth Factor I Insulin-Like Growth Factor II Mammary Neoplasms, Experimental Medroxyprogesterone 17-Acetate Mice Mice, Inbred BALB C Oligonucleotides, Antisense Receptor, IGF Type 1 Receptor, IGF Type 2 Tumor Cells, Cultured Animalia |
| spellingShingle |
somatomedin b somatomedin b receptor somatomedin c somatomedin c receptor animal cell animal experiment animal model animal tissue article breast adenocarcinoma breast epithelium cancer growth cell proliferation controlled study female in situ hybridization mouse nonhuman protein expression Adenocarcinoma Animals Base Sequence Cell Division Female In Situ Hybridization Insulin-Like Growth Factor I Insulin-Like Growth Factor II Mammary Neoplasms, Experimental Medroxyprogesterone 17-Acetate Mice Mice, Inbred BALB C Oligonucleotides, Antisense Receptor, IGF Type 1 Receptor, IGF Type 2 Tumor Cells, Cultured Animalia Involvement of insulin-like growth factors-I and-II and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas |
| topic_facet |
somatomedin b somatomedin b receptor somatomedin c somatomedin c receptor animal cell animal experiment animal model animal tissue article breast adenocarcinoma breast epithelium cancer growth cell proliferation controlled study female in situ hybridization mouse nonhuman protein expression Adenocarcinoma Animals Base Sequence Cell Division Female In Situ Hybridization Insulin-Like Growth Factor I Insulin-Like Growth Factor II Mammary Neoplasms, Experimental Medroxyprogesterone 17-Acetate Mice Mice, Inbred BALB C Oligonucleotides, Antisense Receptor, IGF Type 1 Receptor, IGF Type 2 Tumor Cells, Cultured Animalia |
| description |
The role of the insulin-like growth factors (IGFs) system was investigated in hormone-dependent (HD) and -independent (HI) in vivo lines of the medroxyprogesterone acetate (MPA)-induced mammary tumor model in Balb/c mice. IGF-II protein and message showed a three- to four-fold increase in HD lines growing in MPA-treated mice, as compared with HD tumors growing in untreated mice. Progression to a hormone-independent phenotype in all these lines was accompanied by a high constitutive expression of IGF-II. Similar IGF-I mRNA levels were detected in HD and HI lines. Both IGE-I and -II messages arose from the malignant epithelial cells, as shown by in situ hybridization studies. A significant decrease in Man-6P/type II IGF-R content was detected in HD tumors growing in MPA-treated mice as compared with HD lines growing in untreated mice. On the other hand, in HI tumors, notwithstanding high IGF-II synthesis, the levels of Man-6P/type II IGF-R remain high. Competitive inhibition and affinity labeling studies showed an almost exclusive binding of IGF-II to Man-6P/type II IGF-R on tumor membranes. The involvement of IGFs in the growth of epithelial primary cultures of the C4-HD line was evaluated. Exogenous IGF-I potentiated MPA stimulatory effect at concentrations of 50-100 ng/ml. Treatment of C4-HD cells with antisense oligodeoxynucleotides (ASODNs) to type I IGF-R and to IGF-II RNA resulted in a dose-dependent inhibition of MPA-mediated cell proliferation. The inhibition caused by IGF-II ASODNs could not be overcome by the addition of IGF-II up to 150 ng/ml. ASODNs to type I IGF-R at 40 μg/ml reduced by 75% the number of type I IGF-R; ASODNs to IGF-II at 1 μM decreased by 83% the levels of IGF-II protein. Our results provide support for the involvement of IGE-I and -II in MPA-induced mammary tumor growth by autocrine pathways. |
| title |
Involvement of insulin-like growth factors-I and-II and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas |
| title_short |
Involvement of insulin-like growth factors-I and-II and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas |
| title_full |
Involvement of insulin-like growth factors-I and-II and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas |
| title_fullStr |
Involvement of insulin-like growth factors-I and-II and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas |
| title_full_unstemmed |
Involvement of insulin-like growth factors-I and-II and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas |
| title_sort |
involvement of insulin-like growth factors-i and-ii and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas |
| publishDate |
1998 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09600760_v67_n4_p305_Elizalde http://hdl.handle.net/20.500.12110/paper_09600760_v67_n4_p305_Elizalde |
| _version_ |
1768541662595776512 |