EXPRESSION OF HOXA-1 AND HOXB-7 REGULATED BY EXTRACELLULAR MATRIX-DEPENDENT SIGNALS IN MAMMARY EPITHELIAL-CELLS

Homeobox-containing genes encode transcriptional regulators involved i n cell fate and pattern formation during embryogenesis. Recently, it h as become clear that their expression in continuously developing adult tissues, as well as in tumorigenesis, may be of equal importance. In the mouse mammary gland, expression patterns of several homeobox genes suggest a role in epithelial-stromal interactions. Because the stroma and the extracellular matrix (ECM) are known to influence both functi onal and morphological development of the mammary gland, we asked whet her these genes would be expressed postnatally in the gland and also i n cell lines in culture and whether they could be modulated by ECM. Us ing a polymerase chain reaction-base strategy five members of the Hox gene clusters a and b were shown to be expressed in cultured mouse mam mary cells. Hoxa-1 and Hoxb-7 were chosen for further analysis. Hoxb-7 was chosen because it had not been described previously in the mammar y gland and was modulated at different stages of gland development. Ho xa-1 was chosen because it was reported previously to be expressed onl y in mammary tumors, and not in normal glands. We showed that culturin g the mammary epithelial cell lines SCp2 and CID-9 on a basement membr ane (BM) thai was previously shown to induce a lactational phenotype w as necessary to turn off Hoxb-7 but a change in cell shape, brought ab out by culturing the cells on an inert substratum such as polyHEMA, wa s sufficient to downregulate Hoxa-1. This is the first report of modul ation of homeobox genes by ECM. The results provide a rationale for th e differential pattern of expression in vivo of Hoxa-1 and Hoxb-7 duri ng different stages of development. The culture model should permit fu rther in-depth analysis of the molecular mechanisms involved in how EC M signaling and homeobox genes may interact to bring about tissue orga nization. (C) 1998 Wiley-Liss, Inc.