title: Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer.
abstract: Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors which have been implicated in breast cancer. The aim of this study was to evaluate FGFR-1, -2, -3, and -4 protein expressions in normal murine mammary gland development, and in murine and human breast carcinomas. Using immunohistochemistry and Western blot, we report a hormonal regulation of FGFR during postnatal mammary gland development. Progestin treatment of adult virgin mammary glands resulted in changes in localization of FGFR-3 from the cytoplasm to the nucleus, while treatment with 17-β-estradiol induced changes in the expressions and/or localizations of FGFR-2 and -3. In murine mammary carcinomas showing different degrees of hormone dependence, we found progestin-induced increased expressions, mainly of FGFR-2 and -3. These receptors were constitutively activated in hormone-independent variants. We studied three luminal human breast cancer cell lines growing as xenografts, which particularly expressed FGFR-2 and -3, suggesting a correlation between hormonal status and FGFR expression. Most importantly, in breast cancer samples from 58 patients, we found a strong association (P < 0.01; Spearman correlation) between FGFR-2 and -3 expressions and a weaker correlation of each receptor with estrogen receptor expression. FGFR-4 correlated with c-erbB2 over expression. We conclude that FGFR-2 and -3 may be mechanistically linked and can be potential targets for treatment of estrogen receptor-positive breast cancer patients.
authors: Institute of Experimental Biology and Medicine, CONICET, Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina.
authors: Juan P
authors: JP
authors: Cerliani
authors: Silvia I
authors: SI
authors: Vanzulli
authors: Cecilia Pérez
authors: CP
authors: Piñero
authors: María C
authors: MC
authors: Bottino
authors: Ana
authors: A
authors: Sahores
authors: Myriam
authors: M
authors: Nuñez
authors: Romina
authors: R
authors: Varchetta
authors: Rubén
authors: R
authors: Martins
authors: Eduardo
authors: E
authors: Zeitlin
authors: Stephen M
authors: SM
authors: Hewitt
authors: Alfredo A
authors: AA
authors: Molinolo
authors: Claudia
authors: C
authors: Lanari
authors: Caroline A
authors: CA
authors: Lamb
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008321:Mammary Glands, Animal / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D008875:Middle Aged; D011247:Pregnancy; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3