The association between cyclo-oxygenase-2 expression and cell proliferation and angiogenesis in human breast cancer

Background

Cyclo-oxygenase (COX) is the rate-limiting enzyme in converting arachidonic acid to prostaglandins. There are two isoforms of COX: COX-1, which is expressed in many tissues; and COX-2, which is the inducible form. COX-2 has been reported to be involved in carcinogenesis and tumour angiogenesis. Therefore, we hypothesized that COX-2 expression was associated with that of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) in human breast cancer.

Materials and method

RNA was extracted from 15 human breast carcinomas and adjacent noncancerous tissue (ANCT). COX-2, VEGF189 and PCNA expressions were estimated by reverse transcriptase-PCR (RT-PCR) and Taqman methodology in the RNA samples. The results were analyzed using Spearman's correlation with Student's t-test.

Results

Median mRNA copy number for PCNA mRNA in tumours was 1.65 × 10⁶ (range 3.79 × 10⁵-1.46 × 10⁷). For COX-2, the median mRNA copy number was 4.56 × 10⁵ (range 2.48 × 10³-5.10 × 10⁶) in tumours and 2.26 × 10⁶(range 1.37E+05-4.79E+07) in ANCT. Copy numbers of VEGF mRNA in tumours had a median value of 2.13 × 10⁶ (range 3.42 × 10¹-3.37 × 10⁷). There was a highly significant correlation between COX-2 and PCNA levels in tumours (r's = 0.7896; P = 0.000001) and VEGF in tumour samples (r's = 0.4610; 2 P = 0.0320).

Conclusion

COX-2 expression is significantly associated with increased cellular proliferation and angiogenesis in invasive breast cancer. The upregulation of COX-2 in ANCT suggests that COX-2 in the host is relevant to mammary carcinogenesis.