Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II)

N Brünner; D Yee; F G Kern; M Spang-Thomsen; M E Lippman; K J Cullen

Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II)

N Brünner, D Yee, F G Kern, M Spang-Thomsen, M E Lippman, K J Cullen

Inflammation, Metabolism and Oxidation

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

48 Citationer (Scopus)

Abstract

Udgivelsesdato: 1993-null

Originalsprog	Engelsk
Tidsskrift	European Journal of Cancer
Vol/bind	29A
Udgave nummer	4
Sider (fra-til)	562-9
Antal sider	7
ISSN	0959-8049
Status	Udgivet - 1993

Bibliografisk note

Keywords: Animals; Breast Neoplasms; Down-Regulation; Estradiol; Female; Humans; Insulin-Like Growth Factor II; Mice; Mice, Nude; Mitosis; Neoplasm Transplantation; RNA, Messenger; RNA, Neoplasm; Receptor, IGF Type 2; Tamoxifen; Tumor Cells, Cultured

Citationsformater

@article{80431cf0654e11de8bc9000ea68e967b,

title = "Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II)",

abstract = "Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens for some human breast cancer cell lines, and expression of IGF-II mRNA in the oestrogen receptor-positive (ER+) and oestradiol (E2) stimulated human breast cancer cell line T47D is increased by E2, suggesting a role for IGF-II in the mitogenic response to E2. Very little information is available from the literature on the relation between growth inhibition by endocrine therapy and cellular production of IGF-II. Here we report on the effect of E2 and tamoxifen (TAM) on IGF-II mRNA and protein expression in the ER+T61 human breast cancer xenograft. Growth of the T61 tumour is inhibited by treatment with E2 and TAM. Ribonuclease (RNAse) protection assays with human- and mouse-specific IGF-II antisense probes were used to study the regulation of IGF-II mRNA by E2 and TAM in the tumour. IGF-II protein expression was studied by radioimmunoassay. Untreated T61 tumours have a high baseline expression of IGF-II mRNA. TAM treatment of T61 tumours, which results in inhibition of tumour growth without tumour regression, reduced IGF-II mRNA expression approximately 10-fold after 48 h of treatment. E2 treatment of T61 tumours, which results in tumour regression, was accompanied by a more pronounced decrease in IGF-II mRNA expression in the tumour cells; 96 h after initiation of E2 treatment, there was almost no detectable IGF-II mRNA. Analyses of IGF-II protein showed that both treatments significantly reduced the concentration of IGF-II protein in the tumours. This down-regulation was found to be specific for IGF-II, since analyses of the effect of E2 on the expression of IGF-I mRNA, 36B4 mRNA, transforming growth factor alpha(TGF-alpha) mRNA, and epidermal growth factor (EGF) receptor mRNA in T61 tumours did not reveal any down-regulation. To further study the relation between inhibition of tumour growth and down-regulation of IGF-II, we exposed T61 tumours to a monoclonal antibody, alpha-IR3, which abolishes the physiological effect of IGF-I and IGF-II by blocking the binding of both growth factors to the type I IGF receptor. Treatment with alpha-IR3 resulted in inhibition of tumour growth during treatment.(ABSTRACT TRUNCATED AT 400 WORDS)",

author = "N Br{\"u}nner and D Yee and Kern, {F G} and M Spang-Thomsen and Lippman, {M E} and Cullen, {K J}",

note = "Keywords: Animals; Breast Neoplasms; Down-Regulation; Estradiol; Female; Humans; Insulin-Like Growth Factor II; Mice; Mice, Nude; Mitosis; Neoplasm Transplantation; RNA, Messenger; RNA, Neoplasm; Receptor, IGF Type 2; Tamoxifen; Tumor Cells, Cultured",

year = "1993",

language = "English",

volume = "29A",

pages = "562--9",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Pergamon",

number = "4",

}

TY - JOUR

T1 - Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II)

AU - Brünner, N

AU - Yee, D

AU - Kern, F G

AU - Spang-Thomsen, M

AU - Lippman, M E

AU - Cullen, K J

N1 - Keywords: Animals; Breast Neoplasms; Down-Regulation; Estradiol; Female; Humans; Insulin-Like Growth Factor II; Mice; Mice, Nude; Mitosis; Neoplasm Transplantation; RNA, Messenger; RNA, Neoplasm; Receptor, IGF Type 2; Tamoxifen; Tumor Cells, Cultured

PY - 1993

Y1 - 1993

N2 - Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens for some human breast cancer cell lines, and expression of IGF-II mRNA in the oestrogen receptor-positive (ER+) and oestradiol (E2) stimulated human breast cancer cell line T47D is increased by E2, suggesting a role for IGF-II in the mitogenic response to E2. Very little information is available from the literature on the relation between growth inhibition by endocrine therapy and cellular production of IGF-II. Here we report on the effect of E2 and tamoxifen (TAM) on IGF-II mRNA and protein expression in the ER+T61 human breast cancer xenograft. Growth of the T61 tumour is inhibited by treatment with E2 and TAM. Ribonuclease (RNAse) protection assays with human- and mouse-specific IGF-II antisense probes were used to study the regulation of IGF-II mRNA by E2 and TAM in the tumour. IGF-II protein expression was studied by radioimmunoassay. Untreated T61 tumours have a high baseline expression of IGF-II mRNA. TAM treatment of T61 tumours, which results in inhibition of tumour growth without tumour regression, reduced IGF-II mRNA expression approximately 10-fold after 48 h of treatment. E2 treatment of T61 tumours, which results in tumour regression, was accompanied by a more pronounced decrease in IGF-II mRNA expression in the tumour cells; 96 h after initiation of E2 treatment, there was almost no detectable IGF-II mRNA. Analyses of IGF-II protein showed that both treatments significantly reduced the concentration of IGF-II protein in the tumours. This down-regulation was found to be specific for IGF-II, since analyses of the effect of E2 on the expression of IGF-I mRNA, 36B4 mRNA, transforming growth factor alpha(TGF-alpha) mRNA, and epidermal growth factor (EGF) receptor mRNA in T61 tumours did not reveal any down-regulation. To further study the relation between inhibition of tumour growth and down-regulation of IGF-II, we exposed T61 tumours to a monoclonal antibody, alpha-IR3, which abolishes the physiological effect of IGF-I and IGF-II by blocking the binding of both growth factors to the type I IGF receptor. Treatment with alpha-IR3 resulted in inhibition of tumour growth during treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

AB - Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens for some human breast cancer cell lines, and expression of IGF-II mRNA in the oestrogen receptor-positive (ER+) and oestradiol (E2) stimulated human breast cancer cell line T47D is increased by E2, suggesting a role for IGF-II in the mitogenic response to E2. Very little information is available from the literature on the relation between growth inhibition by endocrine therapy and cellular production of IGF-II. Here we report on the effect of E2 and tamoxifen (TAM) on IGF-II mRNA and protein expression in the ER+T61 human breast cancer xenograft. Growth of the T61 tumour is inhibited by treatment with E2 and TAM. Ribonuclease (RNAse) protection assays with human- and mouse-specific IGF-II antisense probes were used to study the regulation of IGF-II mRNA by E2 and TAM in the tumour. IGF-II protein expression was studied by radioimmunoassay. Untreated T61 tumours have a high baseline expression of IGF-II mRNA. TAM treatment of T61 tumours, which results in inhibition of tumour growth without tumour regression, reduced IGF-II mRNA expression approximately 10-fold after 48 h of treatment. E2 treatment of T61 tumours, which results in tumour regression, was accompanied by a more pronounced decrease in IGF-II mRNA expression in the tumour cells; 96 h after initiation of E2 treatment, there was almost no detectable IGF-II mRNA. Analyses of IGF-II protein showed that both treatments significantly reduced the concentration of IGF-II protein in the tumours. This down-regulation was found to be specific for IGF-II, since analyses of the effect of E2 on the expression of IGF-I mRNA, 36B4 mRNA, transforming growth factor alpha(TGF-alpha) mRNA, and epidermal growth factor (EGF) receptor mRNA in T61 tumours did not reveal any down-regulation. To further study the relation between inhibition of tumour growth and down-regulation of IGF-II, we exposed T61 tumours to a monoclonal antibody, alpha-IR3, which abolishes the physiological effect of IGF-I and IGF-II by blocking the binding of both growth factors to the type I IGF receptor. Treatment with alpha-IR3 resulted in inhibition of tumour growth during treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

M3 - Journal article

C2 - 8435211

SN - 0959-8049

VL - 29A

SP - 562

EP - 569

JO - European Journal of Cancer

JF - European Journal of Cancer

IS - 4

ER -