INVESTIGADORES
SREBROW Anabella
artículos
Título:
Expression of Hoxa-1 and Hoxb-7 is regulated by extracellular matrix-dependent signals in mammary epithelial cells
Autor/es:
SREBROW ANABELLA; FRIEDMANN YAEL; RAVANPAY ALI; DANIEL CHARLES; BISSELL MINA J
Revista:
JOURNAL OF CELLULAR BIOCHEMISTRY
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Año: 1998 vol. 69 p. 377 - 391
ISSN:
0730-2312
Resumen:
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Homeobox-containing
genes encode transcriptional regulators involved in cell fate and pattern
formation during embryogenesis. Recently, it has 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 functional and morphological
development of the mammary gland, we asked whether these genes would be
expressed postnatally in the gland and also in cell lines in culture and
whether they could be modulated by ECM. Using a polymerase chain reaction-base
strategy five members of the Hox gene clusters a and b were shown to be
expressed in cultured mouse mammary cells. Hoxa-1 and Hoxb-7 were chosen for
further analysis. Hoxb-7 was chosen because it had not been described
previously in the mammary gland and was modulated at different stages of gland
development. Hoxa-1 was chosen because it was reported previously to be
expressed only in mammary tumors, and not in normal glands. We showed that
culturing the mammary epithelial cell lines SCp2 and CID-9 on a basement
membrane (BM) that was previously shown to induce a lactational phenotype was
necessary to turn off Hoxb-7, but a change in cell shape, brought about by
culturing the cells on an inert substratum such as polyHEMA, was sufficient to
downregulate Hoxa-1. This is the first report of modulation of homeobox genes
by ECM. The results provide a rationale for the differential pattern of
expression in vivo of Hoxa-1 and Hoxb-7 during different stages of development.
The culture model should permit further in-depth analysis of the molecular mechanisms
involved in how ECM signaling and homeobox genes may interact to bring about
tissue organization.