The role of TGFBI in mesothelioma and breast cancer: association with tumor suppression

Abstract

Background Transforming growth factor β induced (TGFBI) product, an extracellular matrix (ECM) protein, has been implicated as a putative tumor suppressor in recent studies. Our previous findings revealed that expression of TGFBI gene is down-regulated in a variety of cancer cell lines and clinical tissue samples. In this study, ectopic expression of TGFBI was used to ascertain its role as a tumor suppressor and to determine the underlying mechanism of mesothelioma and breast cancer. Methods Cells were stably transfected with pRc/CMV2-TGFBI and pRc/CMV2-empty vector with Lipofectamine Plus. Ectopic expression of TGFBI was quantified by using quantitative PCR and Western-blotting. Characterization of cell viability was assessed using growth curve, clonogenic survival and soft agar growth. The potential of tumor formation was evaluated by an in vivo mouse model. Cell cycle was analyzed via flow cytometry. Expressions of p21, p53, p16 and p14 were examined using Western-blotting. Senescent cells were sorted by using a Senescence β-Galactosidase Staining Kit. Telomerase activity was measured using quantitative telomerase detection kit. Results In this study, an ectopic expression of TGFBI in two types of cancer cell lines, a mesothelioma cell line NCI-H28 and a breast cancer cell line MDA-MB-231 was found to have reduced the cellular growth, plating efficiency, and anchorage-independent growth. The tumorigenicity of these cancer cell lines as determined by subcutaneous inoculation in nude mice was similarly suppressed by TGFBI expression. Likewise, TGFBI expression reduced the proportion of S-phase while increased the proportion of G1 phase in these cells. The redistribution of cell cycle phase after re-expression of TGFBI was correspondent with transiently elevated expression of p21 and p53. The activities of senescence-associated β-galactosidase and telomerase were enhanced in TGFBI-transfected cells. Conclusion Collectively, these results imply that TGFBI plays a suppressive role in the development of mesothelioma and breast cancer cells, possibly through inhibitions of cell proliferation, delaying of G1-S phase transition, and induction of senescence.

TGF-β1 signaling pathway serves a role in HepG2 cell regulation by affecting the protein expression of PCNA, gankyrin, p115, XIAP and survivin

“…Previously, TGF-β1 has been revealed to induce G 1 -phase cell cycle arrest or prolong the time of the G 1 -S phase transition in mesothelioma and breast cancer (38), which is consistent with the results of the present study. In the exogenous TGF-β1 group, cells were arrested in the G 1 phase, and the percentage of cells in the S and G 2 phases decreased.…”

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“…5 and 6), with high levels in untreated compared to treated tumours. The latter response is a trend similar to the results documented in an article by Li et al [33]. Tgfbi may have a dual role; an anti-tumourigenic function in early tumour growth and as a pro-oncogenic supporter in late stage tumours.…”

Extracellular Matrix Proteins Expression Profiling in Chemoresistant Variants of the A2780 Ovarian Cancer Cell Line

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