Differential expression of integrin mRNAs and proteins during normal rat mammary gland development and in carcinogenesis.
A rat model was used to address the roles of integrins in the regulation of normal mammary epithelial cell (MEC) growth and differentiation and in mammary carcinogenesis. The expression of integrins alpha5, alpha6, beta1, and beta4 was examined via Northern and Western blotting analyses in freshly isolated MEC from various postnatal developmental stages. mRNAs for all four integrins were detectable at puberty and were increased during pregnancy. During lactation, the expression of alpha5, alpha6, and beta1 integrin mRNAs reached a peak, whereas that of beta4 integrin decreased dramatically. At day 7 of involution, the levels of all four integrin mRNAs were similar to or slightly higher than that of the pubertal mammary gland. Although alpha5 integrin protein decreased during pregnancy and lactation, beta1 and beta4 integrin proteins had similar profiles as the expression of their respective mRNAs, suggesting that integrin gene expression is regulated at both transcriptional and post-transcriptional levels. All four integrins were heterogeneously expressed in 7,12-dimethylbenz[a]anthracene- and N-nitroso-N-methyl-urea-induced mammary tumors and in RBA and NMU rat mammary tumor cell lines. Adhesion assays showed that isolated MEC interacted with fibronectin to a greater extent than with laminin and collagen I in vitro, and that tumor cells with altered integrin expression exhibited greater adhesive ability to various substrata. Together, our results indicate that alpha5, alpha6, beta1, and beta4 integrins are differentially expressed during normal MEC development and in mammary tumors, supporting the hypothesis that these integrins play important yet complex roles in the mammary gland.
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
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D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000230:Adenocarcinoma / Q000139:chemically induced / Q000196:embryology* / Q000503:physiopathology; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics*; D002273:Carcinogens / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D039482:Integrin alpha5; D039503:Integrin alpha6; D019012:Integrin beta1 / Q000032:analysis / Q000235:genetics; D039663:Integrin beta4; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000196:embryology* / Q000502:physiology*; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000196:embryology* / Q000503:physiopathology; D008770:Methylnitrosourea / Q000494:pharmacology; D009842:Oligopeptides / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000477:Alkylating Agents; D015703:Antigens, CD; D002273:Carcinogens; D016326:Extracellular Matrix Proteins; D039482:Integrin alpha5; D039503:Integrin alpha6; D019012:Integrin beta1; D039663:Integrin beta4; D009842:Oligopeptides; D012333:RNA, Messenger; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea; C047981:arginyl-glycyl-aspartic acid