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

Abstract

We have cloned a human Hevin cDNA from omental adipose tissue of different patients by reverse transcription polymerase chain reaction and shown a sequence variation due to a possible polymorphism at amino acid position 161 (E/G). Hevin protein expressed in vitro showed molecular weights of approximately 75 kDa and 150 kDa, suggesting that Hevin may form a homodimer in vitro. Using Northern blots and a human expressed sequence tAg database analysis, Hevin was shown to be widely expressed in human normal or non-neoplastic diseased tissues with various levels. In contrast to this, its expression was strongly down-regulated in most neoplastic cells or tissues tested. However, neither the mechanism nor the physiological meaning of this down-regulation is known. As an initial step towards investigating the functional role of Hevin in cell growth and differentiation, we transiently or stably expressed this gene in cancer cells (HeLa 3S) that are devoid of endogenous Hevin and measured DNA synthesis (cell proliferation) by 5-bromo-2′-deoxyuridine incorporation. Hevin was shown to be a negative regulator of cell proliferation. Furthermore, we have shown that Hevin can inhibit progression of cells from G1 to S phase or prolong G1 phase. This is the first report which describes the function of Hevin in cell growth and proliferation. Through database analysis, Hevin was found to be located on chromosome 4 which contains loss of heterozygosity of many tumour suppressor genes. Taken together, these results suggest that Hevin may be a candidate for a tumour suppressor gene and a potential target for cancer diagnosis/therapy. © 2000 Cancer Research Campaign

Clinicopathological Significance of Reduced SPARCL1 Expression in Human Breast Cancer

“…In the growth and proliferation of various tumor cells, SPARCL1 often presents decreased expression as a negative regulative factor, which may be closely related to the increase of the cell proliferation activity and the cell cycle progression (Claeskens et al, 2000). Particularly, growing evidence shows that SPARCL1 often presents a reduced or absent expression pattern in a variety of human tumor tissues (Bendik et al, 1998;Nelson et al, 1998;Isler et al, 2004;Esposito et al, 2007;Zaravinos et al, 2011;Hurley et al, 2012;Li et al, 2012).…”

“…The high endothelial venules are special round post-capillary venules as opposed to the flat endothelial cells found in regular venules, and enable high levels of lymphocytes in the blood to enter the lymphatic system. SPARCL1 participates in many physiological functions such as cell proliferation and muscle differentiation, and can promote lymphocyte transportation through adjusting the endothelial cell adhesion function (Girard and Springer, 1996;Claeskens et al, 2000). SPARCL1 is expressed in many tissues and organs such as heart, lung, brain, bone, muscle, colon and lymphatic gland, but it has a lower expression in pancreas, spleen, thyroid gland and placental tissue and even SPARCL1 is not expressed in liver, kidney and peripheral blood leucocytes (Girard and Springer, 1995;Hambrock et al, 2003).…”

“…SPARCL1 is expressed in many tissues and organs such as heart, lung, brain, bone, muscle, colon and lymphatic gland, but it has a lower expression in pancreas, spleen, thyroid gland and placental tissue and even SPARCL1 is not expressed in liver, kidney and peripheral blood leucocytes (Girard and Springer, 1995;Hambrock et al, 2003). Recently, a few of studies have reported that SPARCL1 was down-regulated in a wide variety of human malignancies including lung cancer (Bendik et al, 1998;Isler et al, 2004), prostate cancer (Nelson et al, 1998;Hurley et al, 2012), pancreatic cancer (Esposito et al, 2007), and gastric cancer (Li et al, 2012), and might play a role as a tumor suppressor gene (Claeskens et al, 2000). However, little is known about the expression and significance of SPARCL1 in human breast cancer.…”

Gene expression profiling of human ovarian tumours

“…Although no specific functional data are available, Mok et al (1994) identified DOC1 (downregulated in ovarian cancer) using a DNA-fingerprinting approach to find genes differentially expressed between ovarian cancer cells and normal ovarian epithelial cells. SPARC-like 1 (SPARCL1, MAST9, hevin, SC-1) is a member of the SPARC family (Claeskens et al, 2001). This gene was originally shown to be downregulated in human non-small cell lung cancer and subsequent reports indicated that downregulation of SPARCL1 also occurs in prostate and colon carcinomas (Bendik et al, 1998;Isler et al, 2001).…”

Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome

“…Sparcl1 markedly inhibited prostate epithelial bud elongation; however, comparable expression of proliferation markers in Sparcl1-treated prostate organ cultures suggests that Sparcl1 does not regulate proliferation in the prostate. Because Sparcl1's role in proliferation is varied, we further defined SPARCL1-mediated regulation of prostatic epithelial cell growth (10,18,19). We examined cellular proliferation and death in SPARCL1-treated prostate cells and demonstrated that SPARCL1 did not restrict the growth of multiple prostate cancer cell lines (Fig.…”