Expression of 2 variant forms of fibroblast growth factor receptor 1 in human breast.
The expression of variant mRNAs encoding isoforms of fibroblast growth factor receptor (FGFR)1 with either 2 or 3 Ig-like loops in the extracellular domain was investigated in human breast tissues and cell lines using a polymerase chain reaction amplification method. Almost all tissues contained both forms of FGFR1, but cancers (n = 137) had a significantly lower proportion of the transcript that encoded the full 3-loop form compared with non-malignant biopsies (n = 34). This was confirmed using microdissected populations of normal and cancerous cells from frozen tissue sections. A high ratio of the 2- to 3-loop form was found to be predictive of reduced relapse-free survival. In both groups, however, the predominant form of FGFR1 was that encoding the 2-loop receptor. Cell lines derived from a variety of tissues, including breast, also co-expressed both variants of FGFR1, suggesting their presence within the same cell type. Again, there was a similar preponderance of the shorter isoform. Our results were confirmed at the protein level, where out of 5 cancers analysed 4 expressed more of the 2-loop form than the 3-loop form. Our findings suggest that cells may normally simultaneously express several splice variants of FGFR1, and aberrant expression or a change in their relative amounts (i.e., in malignancy) could contribute to modified responses to either autocrine or paracrine factors.
Luqmani
Y A
YA
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Mortimer
C
C
Yiangou
C
C
Johnston
C L
CL
Bansal
G S
GS
Sinnett
D
D
Law
M
M
Coombes
R C
RC
D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D001483:Base Sequence; D001940:Breast / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor