Hevin is down-regulated in many cancers and is a negative regulator of cell growth and proliferation

We have cloned a human Hevin cDNA from omental adipose tissue of different patients by reverse transcription polymerase chain reaction and shown a seq uence variation due to a possible polymorphism at amino acid position 161 ( E/G). Hevin protein expressed in vitro showed molecular weights of approxim ately 75 kDa and 150 kDa, suggesting that Hevin may form a homodimer in vit ro. Using Northern blots and a human expressed sequence tAg database analys is, Hevin was shown to be widely expressed in human normal or non-neoplasti c diseased tissues with various levels. In contrast to this, its expression was strongly down-regulated in most neoplastic cells or tissues tested. Ho wever, neither the mechanism nor the physiological meaning of this down-reg ulation is known. As an initial step towards investigating the functional r ole of Hevin in cell growth and differentiation, we transiently or stably e xpressed this gene in cancer cells (HeLa 3S) that are devoid of endogenous Hevin and measured DNA synthesis (cell proliferation) by 5-bromo-2'-deoxyur idine incorporation. Hevin was shown to be a negative regulator of cell pro liferation. Furthermore, we have shown that Hevin can inhibit progression o f cells from G1 to S phase or prolong G1 phase. This is the first report wh ich describes the function of Hevin in cell growth and proliferation. Throu gh database analysis, Hevin was found to be located on chromosome 4 which c ontains loss of heterozygosity of many tumour suppressor genes. Taken toget her, these results suggest that Hevin may be a candidate for a tumour suppr essor gene and a potential target for cancer diagnosis/therapy. (C) 2000 Ca ncer Research Campaign.