Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor

E. Fenig; Y. Kanfi; Q. Wang; E. Beery; T. Livnat; L. Wasserman; G. Lilling; J. Yahalom; R. Wieder; J. Nordenberg

doi:10.1023/a:1012522321762

Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor

E. Fenig, Y. Kanfi, Q. Wang, E. Beery, T. Livnat, L. Wasserman, G. Lilling, J. Yahalom, R. Wieder, J. Nordenberg

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Recent studies from our laboratory have revealed that basic fibroblast growth factor (bFGF) selectively inhibits the proliferation of human MCF-7 breast cancer cells. It has also been shown to enhance cis-platinum-induced apoptosis, decrease levels of the anti-apoptotic gene product bcl-2, and increase levels of the cyclin-dependent protein kinase inhibitor p21/WAF1/Cip1. Transforming growth factor beta-1 (TGFβ₁), a cell growth regulator has been found to have an inhibitory effect on breast cancer cells. The aim of the present study was to evaluate the possible role of TGFβ₁ in the antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGFβ₁ mRNA expression in the cells and enhanced the secretion of TGFβ₁ into culture medium. However, exogenous addition of TGFβ₁ neither led to a decrease in bcl-2 nor induced an increase in the levels of p21/WAF1/Cip1 and neutralizing antibodies to TGFβ₁, did not reverse bFGF-induced G₁ arrest nor the increase in p21/WAF1/Cip1 level. In contrast, antisense oligonucleotides to TGFβ₁ abrogated the antiproliferative effects and inhibited the induction of p21/WAF1/Cip1 by bFGF in MCF-7 cells. These data suggest that the anti-proliferative effects of bFGF in human MCF-7 breast cancer cells are mediated by endogenous TGFβ₁, while exogenous TGFβ₁ does not mimic all the effects of bFGF on these breast cancer cells. These findings provide an important basis for further investigations into the autocrine and paracrine processes that control the growth of breast cancer cells.

Original language	English
Pages (from-to)	27-37
Number of pages	11
Journal	Breast Cancer Research and Treatment
Volume	70
Issue number	1
DOIs	https://doi.org/10.1023/a:1012522321762
State	Published - Nov 2001
Externally published	Yes

Bibliographical note

Funding Information:
We are grateful for the editorial and secretarial help of Mrs Gloria Ginzach and Mrs Melanie Kawe. Eyal Fenig was supported by Israel Cancer Research Association, a donation by Mrs. Silvia Kaplan, in memory of Henry Kaplan, a grant from the Chief Scientist, Israel Ministry of Health, and Fingerhut Fund, Tel Aviv University, Israel; and Robert Wiederof was supported by the US Army Breast Cancer Research Program (DAMD17-94-J-4463) and author Qin Wang was supported by the State of New Jersey Commission on Cancer Research Outstanding Breast Cancer Research Fellowship Award.

Keywords

Basic fibroblast growth factor
Breast cancer
Transforming growth factor beta
bcl-2
p21/WAF1/Cip1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1023/a:1012522321762

Cite this

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title = "Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor",

abstract = "Recent studies from our laboratory have revealed that basic fibroblast growth factor (bFGF) selectively inhibits the proliferation of human MCF-7 breast cancer cells. It has also been shown to enhance cis-platinum-induced apoptosis, decrease levels of the anti-apoptotic gene product bcl-2, and increase levels of the cyclin-dependent protein kinase inhibitor p21/WAF1/Cip1. Transforming growth factor beta-1 (TGFβ1), a cell growth regulator has been found to have an inhibitory effect on breast cancer cells. The aim of the present study was to evaluate the possible role of TGFβ1 in the antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGFβ1 mRNA expression in the cells and enhanced the secretion of TGFβ1 into culture medium. However, exogenous addition of TGFβ1 neither led to a decrease in bcl-2 nor induced an increase in the levels of p21/WAF1/Cip1 and neutralizing antibodies to TGFβ1, did not reverse bFGF-induced G1 arrest nor the increase in p21/WAF1/Cip1 level. In contrast, antisense oligonucleotides to TGFβ1 abrogated the antiproliferative effects and inhibited the induction of p21/WAF1/Cip1 by bFGF in MCF-7 cells. These data suggest that the anti-proliferative effects of bFGF in human MCF-7 breast cancer cells are mediated by endogenous TGFβ1, while exogenous TGFβ1 does not mimic all the effects of bFGF on these breast cancer cells. These findings provide an important basis for further investigations into the autocrine and paracrine processes that control the growth of breast cancer cells.",

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author = "E. Fenig and Y. Kanfi and Q. Wang and E. Beery and T. Livnat and L. Wasserman and G. Lilling and J. Yahalom and R. Wieder and J. Nordenberg",

note = "Funding Information: We are grateful for the editorial and secretarial help of Mrs Gloria Ginzach and Mrs Melanie Kawe. Eyal Fenig was supported by Israel Cancer Research Association, a donation by Mrs. Silvia Kaplan, in memory of Henry Kaplan, a grant from the Chief Scientist, Israel Ministry of Health, and Fingerhut Fund, Tel Aviv University, Israel; and Robert Wiederof was supported by the US Army Breast Cancer Research Program (DAMD17-94-J-4463) and author Qin Wang was supported by the State of New Jersey Commission on Cancer Research Outstanding Breast Cancer Research Fellowship Award.",

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doi = "10.1023/a:1012522321762",

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AU - Beery, E.

AU - Livnat, T.

AU - Wasserman, L.

AU - Lilling, G.

AU - Yahalom, J.

AU - Wieder, R.

AU - Nordenberg, J.

N1 - Funding Information: We are grateful for the editorial and secretarial help of Mrs Gloria Ginzach and Mrs Melanie Kawe. Eyal Fenig was supported by Israel Cancer Research Association, a donation by Mrs. Silvia Kaplan, in memory of Henry Kaplan, a grant from the Chief Scientist, Israel Ministry of Health, and Fingerhut Fund, Tel Aviv University, Israel; and Robert Wiederof was supported by the US Army Breast Cancer Research Program (DAMD17-94-J-4463) and author Qin Wang was supported by the State of New Jersey Commission on Cancer Research Outstanding Breast Cancer Research Fellowship Award.

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N2 - Recent studies from our laboratory have revealed that basic fibroblast growth factor (bFGF) selectively inhibits the proliferation of human MCF-7 breast cancer cells. It has also been shown to enhance cis-platinum-induced apoptosis, decrease levels of the anti-apoptotic gene product bcl-2, and increase levels of the cyclin-dependent protein kinase inhibitor p21/WAF1/Cip1. Transforming growth factor beta-1 (TGFβ1), a cell growth regulator has been found to have an inhibitory effect on breast cancer cells. The aim of the present study was to evaluate the possible role of TGFβ1 in the antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGFβ1 mRNA expression in the cells and enhanced the secretion of TGFβ1 into culture medium. However, exogenous addition of TGFβ1 neither led to a decrease in bcl-2 nor induced an increase in the levels of p21/WAF1/Cip1 and neutralizing antibodies to TGFβ1, did not reverse bFGF-induced G1 arrest nor the increase in p21/WAF1/Cip1 level. In contrast, antisense oligonucleotides to TGFβ1 abrogated the antiproliferative effects and inhibited the induction of p21/WAF1/Cip1 by bFGF in MCF-7 cells. These data suggest that the anti-proliferative effects of bFGF in human MCF-7 breast cancer cells are mediated by endogenous TGFβ1, while exogenous TGFβ1 does not mimic all the effects of bFGF on these breast cancer cells. These findings provide an important basis for further investigations into the autocrine and paracrine processes that control the growth of breast cancer cells.

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Role of transforming growth factor beta in the growth inhibition of human breast cancer cells by basic fibroblast growth factor

Abstract

Bibliographical note

Keywords

UN SDGs

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