A. Claeskens et al., Hevin is down-regulated in many cancers and is a negative regulator of cell growth and proliferation, BR J CANC, 82(6), 2000, pp. 1123-1130
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.