{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:42:15Z","timestamp":1778683335235,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":3779,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1994,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have explored the relationship of changes in proliferative responses of human mammary epithelial cells to a phorbol ester (TPA) and to 8\u2010Br\u2010cAMP, which modulate the activities of protein kinases A and C (PKA and PKC), with breast tumour progression. Treatment with TPA had no effect on nontumorigenic cell lines established from human fibrocystic biopsies and apparently normal tissue around a tumour. In contrast, TPA strongly inhibited the proliferation of numerous human tumorigenic breast cell lines. Treatment with 8\u2010Br\u2010cAMP decreased the proliferation of all studied nontumorigenic and tumorigenic cell lines. We have also studied the effect of TPA and 8\u2010Br\u2010cAMP on growth of epithelial cells in short\u2010term culture obtained from surgical human mammary biopsies with different states of breast disease. Both drugs enhanced growth of normal breast cells but had no significant effects on cells from biopsies with benign breast disease. In contrast, all examined cuitures from breast cancer biopsies were strongly inhhited by 8\u2010Br\u2010cAMP. Otherwise, TPA had an inhibitory effect only in the case of invasive ductal carcinoma of grade III. Malignant Ha\u2010ras\u2010transformation of nontumorigenic TPA\u2010insensitive breast HBL\u2010100 cells induced an inhibitory effect of TPA. In addition, a TPA\u2010insensitive MCF7 clone was much less tumorigenic in athymic mice than the parental strain shown to be inhibited by TPA. These data suggest that the two intracellular transduction pathways change at different stages of breast pathogenesis. Alterations in the PKA pathway are early events and are probably important to cell immortalization but do not necessarily lead to malignant development. In contrast, changes in PKC pathway are rather later events associated with advanced malignant transformation. \u00a9 1994 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.1041610105","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T04:54:21Z","timestamp":1109393661000},"page":"31-38","source":"Crossref","is-referenced-by-count":23,"title":["Proliferative responses of epithelial cells to 8\u2010bromo\u2010cyclic AMP and to a phorbol ester change during breast Pathogenesis"],"prefix":"10.1002","volume":"161","author":[{"given":"Anna B.","family":"Starzec","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Spanakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alissar","family":"Nehme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Salle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Veber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Mainguene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Planchon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie","family":"Valette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregoire","family":"Prevost","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucien","family":"Israel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(91)90124-P"},{"key":"e_1_2_1_3_1","first-page":"7351","article-title":"Tumor progression in four mammary epithelial cell lines derived from the same patient","volume":"50","author":"Band V.","year":"1990","journal-title":"Cancer Res."},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6269181"},{"key":"e_1_2_1_5_1","first-page":"7093","article-title":"Role of cyclic AMP receptor proteins in growth, differentiation, and suppression of malignancy: New Approaches to therapy","volume":"50","author":"Cho\u2010Chung Y. 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