The rat gene homologous to the human gene 9-27 is involved in the development of the mammary gland.
We have developed a model system for studying differentiation in the mammary gland, by using two clonal cultures deriving from a rat breast adenocarcinoma. They differ in the ability to form domes, structures the significance of which is unknown. By using the subtractive cDNA library approach, we isolated a cDNA that is highly expressed in the dome-forming cells, and identical to the rat8 gene and highly homologous to the human 9-27 gene. Antisense treatment of the dome-forming cells specifically and reproducibly abolishes dome formation, while forced expression of the gene in non-dome-forming cells causes morphological changes suggestive of "flat" domes. In situ hybridization on rat tissues shows that the gene is expressed in epithelia, especially in those forming tubular structures, suggesting a relatedness between these structures and domes. Cytokeratin 8 and E cadherin are strongly expressed in the domes but not outside them, suggesting that the rat8 gene triggers the cells to express molecules that tighten the lateral connections between the cells; the process is likely to parallel that occurring during the differentiation of the mammary gland.
Zucchi
I
I
Istituto di Tecnologie Biomediche Avanzate, Consiglio Nazionale delle Ricerche, Via Ampere 56, 20131 Milan, Italy. zucchi@itba.mi.cnr.it
Montagna
C
C
Susani
L
L
Vezzoni
P
P
Dulbecco
R
R
D000818:Animals; D015415:Biomarkers; D015820:Cadherins / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells; D018076:DNA, Complementary / Q000737:chemistry; D016208:Databases, Factual; D005260:Female; D015723:Gene Library; D005796:Genes; D006801:Humans; D017403:In Situ Hybridization; D007633:Keratins / Q000032:analysis; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development*; D005810:Multigene Family; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D015820:Cadherins; D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D007633:Keratins