Transforming growth factor-β2 (TGF-β2) and -β3 mRNA expressions were studied in ductal hormone-dependent (HD) and -independent (HI) in vivo lines of the medroxyprogesterone acetate (MPA)-induced mammary tumor model in Balb/c mice. MPA treatment of HD tumors induced a significant decrease in TGF-β2 and -β3 mRNA levels. Progression to an HI phenotype of ductal tumors was associated with reduced TGF-β2 and -β3 expressions, as compared with their HD counterparts. Exogenously added TGF-β1, -β2, and -β3 (1 ng/ml) inhibited the proliferation of primary cultures of epithelial cells from ductal HD and HI tumors. In addition, TGF-β expression and effects were studied in the other type of MPA-induced mammary tumors, which are of lobular origin and lack steroid hormone receptors and evidence an HI behavior. These lobular HI lines showed TGF-β2 levels similar to those found in HD lines growing in MPA-treated mice. In contrast, TGF-β3 mRNA levels were 12- to 20-fold higher than in HD tumors. Primary cultures of lobular HI epithelial cells required either TGF-β concentrations of 10 ng/ml to show an inhibitory response, or were completely resistant to TGF-β inhibition. Studies of the molecular mechanisms involved in reduction or loss of TGF-β responsiveness in q HI tumors showed that cell surface type II TGF-β receptor levels were lower in these tumors than those present in HD tumors. Our results support the hypothesis that TGF-β could play a role as an autocrine growth inhibitor in HD and HI ductal tumors. Autonomous growth of lobular HI tumors could be favored by undetectable or low TGF-β1 and -β2 expressions and by reduced or lost sensitivity of epithelial cells to TGF-β's antiproliferative effects. However, the extremely high levels of TGF-β3 expression in lobular HI tumors, in spite of reduced sensitivity to TGF-β3 inhibitory growth effect in tumor epithelial cells, suggest a net positive role for TGF-β3 in these tumors.
Documento: | Artículo |
Título: | Differential expression of and responsiveness to transforming growth factor-β (TGF-β) isoforms in hormone-dependent and independent lines of mouse mammary tumors |
Autor: | Viegas, M.H.; Salatino, M.; Goin, M.; Peters, G.; Labriola, L.; Costa da Cunha, J.; Lanari, C.; Charreau, E.H.; Elizalde, P.V. |
Filiación: | Molec. Mech. of Carcinogenesis Lab., Inst. di Biol. y Med. Experimental, Obligado 2490, Buenos Aires 1428, Argentina |
Palabras clave: | -132; And -β3; Mammary adenocarcinomas; Progestins; Transforming growth factors-β1; cyclin D1; isoprotein; messenger RNA; transforming growth factor beta; affinity labeling; animal; article; Bagg albino mouse; cell culture; epithelium cell; experimental neoplasm; female; fibroblast; gene expression regulation; metabolism; mouse; neoplasm; Northern blotting; Affinity Labels; Animals; Blotting, Northern; Cyclin D1; Epithelial Cells; Female; Fibroblasts; Gene Expression Regulation, Neoplastic; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neoplasms, Hormone-Dependent; Protein Isoforms; RNA, Messenger; Transforming Growth Factor beta; Tumor Cells, Cultured |
Año: | 1999 |
Volumen: | 23 |
Número: | 5 |
Página de inicio: | 375 |
Página de fin: | 386 |
DOI: | http://dx.doi.org/10.1046/j.1525-1500.1999.99038.x |
Título revista: | Cancer Detection and Prevention |
Título revista abreviado: | Cancer Detect. Prev. |
ISSN: | 0361090X |
CODEN: | CDPRD |
CAS: | Affinity Labels; Cyclin D1, 136601-57-5; Protein Isoforms; RNA, Messenger; Transforming Growth Factor beta |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0361090X_v23_n5_p375_Viegas |