T1, an immunoglobulin superfamily member, is expressed in H-ras-dependent epithelial tumours of mammary cells.
T1 is a glycosylated protein in the carcinoembryonic antigen (CEA) family of tumour marker molecules. It was originally identified by virtue of its transient induction after the expression of p21H-ras in NIH3T3 fibroblasts. Here we show that the T1 gene is activated in mammary adenocarcinomas of transgenic mice harbouring an H-ras transgene under the control of the mammary-specific whey acidic protein (WAP) promoter. By contrast, T1 mRNA was not, or only faintly, detectable in mammary carcinomas of transgenic mice bearing a WAP-myc transgene. Thus, T1 overexpression does not appear to be a general tumour-specific phenomenon. A dependence of T1 gene expression on the action of p21H-ras is suggested by the observation of T1 mRNA in nude mouse tumours generated from H-ras-transformed cultured mammary epithelial cells. Interestingly, activation of the T1 gene is also found during the maturation of the mammary gland (3-4 weeks after birth), whereas it is absent during its terminal differentiation in pregnancy and lactation. This expression pattern suggests a role for the secreted T1 glycoprotein in the phase of epithelial proliferation of the mammary gland. It appears that p21H-ras-induced transformation of mammary epithelial cells mimics the situation occurring in puberty. In both developmental stages the T1 glycoprotein might affect cell interactions of the proliferating epithelial cells with the surrounding stroma. It might thus promote ductal outgrowth in gland maturation as well as invasive growth of p21H-ras-transformed mammary epithelial cells.
Rössler
U
U
Department of Cell Chemistry, GSF-Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany.
Andres
A C
AC
Reichmann
E
E
Schmahl
W
W
Werenskiold
A K
AK
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D015870:Gene Expression; D016259:Genes, myc; D011905:Genes, ras; D006023:Glycoproteins / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; D008894:Milk Proteins; D012333:RNA, Messenger; C024471:whey acidic proteins