{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:43:27Z","timestamp":1761155007488},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,7,17]],"date-time":"2006-07-17T00:00:00Z","timestamp":1153094400000},"content-version":"vor","delay-in-days":4128,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[1995,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have studied the influence of synthetic progestins on the estrogen\u2010induced proliferation and type\u2010\u03b2 transforming\u2010growth\u2010factor (TGF\u2010\u03b2) production of 3 breast\u2010tumor cell lines. In long\u2010term growth experiments, progestins inhibited proliferation of T47D cells, while a specific T47D variant and MCF7 cells were not affected, despite the presence of functional progesterone receptors. The effect of progestins was biphasic, since an initial stimulation of proliferation was followed by a prolonged inhibition. This response suggests the involvement of a progestin\u2010induced negative growth regulator. We show here that TGF\u2010\u03b2s do not fulfill this role since (i) the progestin\u2010induced T47D cells are not sensitive to TGF\u2010\u03b2I, \u2010\u03b22 or \u2010\u03b23, (ii) secretion of TGF\u2010\u03b2s is decreased by progestins in all 3 cell lines, and (iii) TGF\u2010\u03b2 neutralizing antibodies do not reverse progestin\u2010induced growth inhibition. Furthermore, evidence was obtained that medium conditioned by T47D cells does not contain any other growth inhibitor to which this cell line responds in a negative autocrine manner. In contrast, MCF7 cells are growth\u2010inhibited by all 3 TGF\u2010\u03b2 isoforms, but are not growth\u2010inhibited by progestins, suggesting that there is no correlation between growth inhibition by progestins and responsiveness to and production of TGF\u2010\u03b2 <jats:italic>in vitro.<\/jats:italic> Although TGF\u2010\u03b2 is a strong growth inhibitor of normal mammary tissue, recent evidence suggests that, in malignant tissue, enhanced TGF\u2010\u03b2 secretion correlates with increased malignancy. Therefore, a progestin\u2010induced decrease in TGF\u2010\u03b2 production, as observed here, may lead to enhanced proliferation of normal but not malignant mammary epithelium. \u00a9 <jats:italic>1995 Wiley\u2010Liss, Inc<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/ijc.2910610114","type":"journal-article","created":{"date-parts":[[2007,2,20]],"date-time":"2007-02-20T00:38:43Z","timestamp":1171931923000},"page":"80-86","source":"Crossref","is-referenced-by-count":27,"title":["The role of TGF\u2010\u03b2 production in growth inhibition of breast\u2010tumor cells by progestins"],"prefix":"10.1002","volume":"61","author":[{"given":"Eric","family":"Kalkhoven","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Kwakkenbos\u2010Isbr\u00fccker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine L.","family":"Mummery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siegfried W.","family":"De Laat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana J. M.","family":"Van Den Eijnden\u2010Van Raaij","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul T.","family":"Van Der Saag","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart Van Der","family":"Burg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,17]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-4-6-821"},{"key":"e_1_2_1_3_1","first-page":"299","article-title":"Differential regulation of expression of the three transforming growth factor \u03b2 species in human breast cancer cell lines by estradiol","volume":"50","author":"Arrick B. A.","year":"1990","journal-title":"Cancer Res."},{"key":"e_1_2_1_4_1","first-page":"193","article-title":"Transforming growth factor \u03b21 can induce estrogen\u2010independent tumorigenicity of human breast cancer cells in athymic mice","volume":"4","author":"Arteaga C. L.","year":"1993","journal-title":"Cell Growth Diff."},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-11-2-266"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/1040-8428(92)90062-U"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(89)90409-3"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114983"},{"key":"e_1_2_1_9_1","first-page":"381","article-title":"Immunocytochemical localization of secreted transforming growth factor\u2010\u03b2 to the advancing edges of primary tumors and to lymph node metastases of human mammary carcinoma","volume":"143","author":"Dalal B. I.","year":"1993","journal-title":"J. Pathol."},{"key":"e_1_2_1_10_1","first-page":"493","article-title":"Resistance to inhibition of cell growth by transforming growth factor\u2010\u03b2 and its role in oncogenesis","volume":"4","author":"Fynan T. M.","year":"1993","journal-title":"Crit. Rev. Oncogen."},{"key":"e_1_2_1_11_1","first-page":"6949","article-title":"Immunohistochemical staining for transforming growth factor \u03b21 associated with disease progression in human breast cancer","volume":"52","author":"Gorsch S. M.","year":"1992","journal-title":"Cancer Res."},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-8-1120"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(94)90096-5"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00683189"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90193-0"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90918-5"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-3-4-611"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.10.5032"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-49295-2_8"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3474783"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041560205"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1991.140"},{"key":"e_1_2_1_23_1","first-page":"6269","article-title":"Production of and responsiveness to transforming growth factor\u2010\u03b2 in normal and oncogene\u2010transformed human mammary epithelial cells","volume":"49","author":"Valverius E. M.","year":"1989","journal-title":"Cancer Res."},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(88)80004-4"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041340112"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.19.7678"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.2910610114","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.2910610114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T20:45:48Z","timestamp":1698353148000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.2910610114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,3,29]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1995,3,29]]}},"alternative-id":["10.1002\/ijc.2910610114"],"URL":"https:\/\/doi.org\/10.1002\/ijc.2910610114","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,3,29]]}}}