Protein arrests cervical cancer growth
Wednesday, 26 November, 2008
A transforming growth factor involved in cell differentiation has been shown to arrest the growth of cervical cancer cells by inhibiting the activity of the enzyme telomerase in a mouse model, Monash University researchers report.
Bone morphogenetic protein-7 (BMP7) is a member of the transforming growth factor beta (TGF-beta) superfamily and normally plays a role in osteoblast differentiation. It has also been shown to inhibit cancer cell proliferation in myeloma and prostate cancer cells, and to inhibit breast and prostate cancer metastasis.
No one is quite sure why this is the case, but the Monash team, led by Associate Professor Jun-Ping Liu of the university’s Department of Immunology, hypothesised that the TGF-beta family may reduce expression of hTERT, the human telomerase reverse transcriptase that is one of the three components of telomerase.
In a paper published recently in Cancer Research, the Monash team has shown that BMP7 inhibits telomerase activity in cervical cancer cells, leading to telomere shortening and thus to cancer cell senescence and apoptosis.
The study involved both in vitro and tumour xenograft experiments. “A single application of recombinant BMP7 produces a significant inhibition of telomerase activity critical in telomere maintenance in cultured cervical cancer HeLa cells,” the researchers report.
“Continuous applications of BMP7 on every second day for two weeks in HeLa cell cultures or xenograft tumours result in sustained depression of telomerase activity and shortening of telomeres.”
They also showed that BMP7 induces increased cell cycle checkpoint activity by the tumour suppressor genes p16 and p53.
Lead author Lucy Cassar, a PhD student, said in a press release that while telomerase is found in healthy cells, BMP7 only interfered with telomerase in the cancer cells.
“Bone Morphogenetic Protein-7 Inhibits Telomerase Activity, Telomere Maintenance, and Cervical Tumor Growth” is published in Cancer Research [doi:10.1158/0008-5472.CAN-08-1323].
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