No abstract

Summary The expression of basic fibroblast growth factor (bFGF) and two of its receptors, FGFR1 and FGFR2, was detected using the polymerase chain reaction, and quantified by comparison to the relative amount of product obtained following co-amplification of the ubiquitous glyceraldehyde phosphate dehydrogenase transcript. Varying levels were found in the vast majority of both cancer and non-malignant breast biopsies as well as in samples of several other normal human tissues. Significantly less bFGF was present in cancers (P< 0.0001). Similarly, FGFR2 product was also much less in cancer tissues (P = 0.0078), as was FGFR1 (P = 0.002). FGFR1 levels in cancers tended to be higher in those which were oestrogen receptor positive (P<0.06). Amplification of different coding regions showed evidence of variant forms of FGFR1 RNA. Cancers appeared to have a significantly greater proportion of PCR product corresponding to the region between the third immunoglobulin like domain and the tyrosine kinase domain (P = 0.046). Differential expression was observed in breast cell lines, with bFGF in the normal derived HBL100, HBR SVI.6.1 and 184A1 but little or none in ZR-.75-1, MCF-7, T47D and MDA-MB-231. FGFR1 was present in most of these but FGFR2 was absent from T47D, MDA-MB-231 and HBL100. ZR-75-1 cells had a marked preponderance of FGFRI variants lacking part of the coding sequence.Aberrant receptor processing may provide clues concerning the role of FGF's and their potential involvement in malignancy.

In order to isolate and characterize genes whose expression may be altered in breast malignancy, we screened a cDNA library with a polyclonal anti-serum against breast-cancer-metastasis membranes and isolated several immunopositive clones. One of these, AJ1, was analyzed in detail and found to be expressed at varying levels as a 3.3-kb mRNA in all of 143 breast cancers. High expression was associated with lymph-node involvement (p = 0.03). Comparison between high- and low-expressing groups showed a significant difference at 4 and 6 years for both overall (p = 0.004 and p = 0.002 respectively) and disease-free (p = 0.0001 and p = 0.04 respectively) survival, but not at 11 years. AJ1 was expressed at much lower levels in non-malignant biopsies as compared with malignant tissue (p = 0.001). Expression was observed in breast-cancer cell lines MCF-7, ZR-75-1, T47D, MDA-MB-231 and HBL 100. Partial sequence analysis of the 620 bp clone showed complete homology with human heat-shock protein 89 alpha. In addition to being heat-inducible in all the breast cell lines examined, AJ1 levels were increased by estradiol (blocked by cyclohexamide and tamoxifen), EGF, oxytocin and vasopressin in a time-dependent manner in MCF-7 cells and by estradiol, EGF, prolactin and hydrocortisone in T47D cells. In MDA-MB-231 cells, EGF caused down-regulation of AJ1 mRNA levels. The increasing evidence for the association of heat-shock proteins with steroid receptors suggests that AJ1 may play an important role in the control of estrogen-receptor transcriptional activity in breast cancers.

Summary This paper examines the expression of fibroblast growth factor 2 (FGF-2) in the malignant human breast. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assess the level of expression of FGF-2 in a series of 51 patients clinically followed up for a median of 84 months (Luqmani et al, 1992

Summary The level of expression of keratinocyte growth factor (KGF) mRNA has been measured in human breast cell lines, purified populations of epithelial cells, myoepithelial cells and fibroblasts from reduction mammoplasty tissue and a panel of 42 breast cancers and 30 non-malignant human breast tissues using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) procedure. We found similar levels of KGF mRNA in malignant and non-malignant breast tissues. The study of the amount of KGF mRNA in breast cell lines and purified populations of cells revealed that fibroblasts are the predominant source of KGF with malignant and non-malignant epithelial cells containing very low levels of KGF mRNA. We have examined the distribution of fibroblast growth factor receptor (FGFR)-2-lllb, which is a highaffinity receptor for KGF and find that it is present on malignant and non-malignant epithelial cells. The level of FGFR-2-lllb present on breast cancer cell lines was sufficient for KGF stimulation of breast cancer cell proliferation. Other members of the fibroblast growth factor family have been either not expressed in the human breast (FGF3, FGF4) or have been found at much reduced levels in breast cancer (FGF1, FGF2) and this is the first member of the family to potentially influence the progression of breast cancer through stimulation of cell division.