Characterization of GRO alpha, beta and gamma expression in human colonic tumours: potential significance of cytokine involvement.

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: GRO alpha, GRO beta, and GRO gamma: GRO beta and GRO gamma share 90 and 86% sequence homology with GRO alpha. The GRO alpha gene product shares homology with, and is melanocyte growth stimulatory activity (MGSA). The MGSA/GRO alpha has potent chemotactic, growth regulatory and transformative functions. The function of GRO beta and gamma is unknown. Expression of GRO alpha is well characterized in vitro; studies in actual human tissues are not reported. We chose to determine the specific expression of GRO alpha, beta and gamma 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 GRO alpha, beta and gamma expressions were determined by polymerase chain reaction (PCR). GRO alpha expression was evaluated in the tumour specimens compared with normal, while there was constitutive expression of GRO gamma in both normal and neoplastic colonic mucosa. Expression of GRO beta was minimal in all tissue specimens. In addition, HT29 colon carcinoma cells stimulated with IL-1 beta and TNF alpha demonstrated induction of GRO alpha and IL-8. Thus, GRO alpha is differently elevated in in vivo colon carcinoma specimens. GRO gamma was constitutively expressed in colonic tissues; GRO beta was not similarly expressed.