Expression of vascular endothelial growth factor, hypoxia inducible factor 1α, and carbonic anhydrase IX in human tumours

Abstract

Aims:To measure vascular endothelial growth factor (VEGF-A) mRNA in a large, diverse cohort of tumours and to investigate whether VEGF-A expression is associated with markers of hypoxia, including hypoxia inducible factor 1α (HIF-1α) and carbonic anhydrase IX (CA9).Methods:The expression of VEGF-A and CA9 was assessed in 5067 fresh frozen human tissue samples and 238 cell lines by DNA microarray analysis. In addition, tissue microarrays were constructed from 388 malignancies to investigate the expression of VEGF-A and HIF-1α by in situ hybridisation and immunohistochemistry, respectively.Results:VEGF-A was significantly upregulated in primary malignancies of the breast, cervix, colon and rectum, oesophagus, head and neck, kidney, ovary, skin, urinary system, and white blood cells by DNA microarray analysis. However, VEGF-A expression only correlated with CA9 expression in renal tissues. In the tissue microarrays, HIF-1α positive cores showed a significant increase in VEGF-A expression in lung, ovary, soft tissue, and thyroid malignancies.Conclusions:The expression of VEGF-A is upregulated in a large proportion of human malignancies, and may be associated with markers of hypoxia. VEGF-A expression can be induced in the absence of hypoxia and hypoxia does not always provoke VEGF-A upregulation in tumours.

Expression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer

“…In addition, HIF-1a expression was only observed in cell nuclei when present ( Figure 1A), as previously described (Jubb et al, 2004). The expression of HIF-2a by neoplastic cells was predominantly cytoplasmic, with nuclear expression in a proportion of cases ( Figure 1B; Talks et al, 2000).…”

P53 in blind subterranean mole rats – loss-of-function versus gain-of-function activities on newly cloned Spalax target genes

“…Our previous results (Avivi et al, 1999) indicated that Spalax VEGF expression is similar to its expression in cancer growths (Jubb et al, 2004;Kuramochi et al, 2006), for example, it is constitutively expressed in maximal levels under normoxia with no further increase under hypoxia. This observation, in fact, triggered our interest in studying Spalax p53 in an effort to use this non-tumoral, hypoxia-adaptive model to study evolutionary changes in p53, analogous to acquired tumoral p53 mutations.…”

Serum Vascular Endothelial Growth Factor-A (VEGF-A) as a Biomarker in Squamous Cell Carcinoma of Head and Neck Patients Undergoing Chemoradiotherapy

“…A decrease in serum VEGF-A level after cancer surgery has been reported in breast cancer (Tang et al, 2011) and in ovarian cancer (Färkkilä et al, 2011). Jubb et al (2004), observed that VEGF-A is significantly upregulated in various malignancies including SCCHN. Based on these observations, we have tried to evaluate the predictive significance of serum VEGF-A level in SCCHN undergoing radio-chemotherapy.…”