Abstract

Abstract

The GRO genes, isolated from transformed fibroblasts, belong to a superfamily of genes such as platelet factor 4 and neutrophil activating peptide/IL-8. Three related GRO genes are described which are closely linked on chromosome 4: GROα, GROβ, and GROγ: GROβ and GROγ share 90 and 86% sequence homology with GROα. The GROα gene product shares homology with, and is melanocyte growth stimulatory activity (MGSA). The MGSA/GROα has potent chemotactic, growth regulatory and transformative functions. The function of GROβ and γ is unknown. Expression of GROα is well characterized in vitro: studies in actual human tissues are not reported. We chose to determine the specific expression of GROα, β and γ in both normal and transformed human colonic tissues and to assess the role of exogenous cytokines on their induction. Tissues from ten patients with colonic neoplasia were obtained at the time of colectomy. All specimens underwent Northern analysis for GRO gene expression, comparing normal colonic mucosa with neoplastic mucosa. Differential GROα, β and γ expressions were determined by polymerase chain reaction (PCR). GROα expression was evaluated in the tumour specimens compared with normal, while there was constitutive expression of GROγ in both normal and neoplastic colonic mucosa. Expression of GROβ was minimal in all tissue specimens. In addition, HT29 colon carcinoma cells stimulated with IL-1β and TNFα demonstrated induction of GROα and IL-8. Thus, GROα is differently elevated in in vivo colon carcinoma specimens. GROγ was constitutively expressed in colonic tissues; GROβ was not similarly expressed. Exogenous cytokines such as IL-1β and TNFα may play a role in the specificity of GRO expression, and also stimulate related genes in this superfamily. This overexpression of GROα may contribute to the transformative potential of human colonic carcinoma.