Changes in
phospholipid and
fatty acid profile are hallmarks of
cancer progression. Increase in peripheral
benzodiazepine receptor expression has been implicated in
breast cancer. The
benzodiazepine,
Ro5-4864, increases cell proliferation in some
breast cancer cell lines. Biosynthesis of
phosphatidylcholine (PC) has been identified as a marker for cells proliferating at high rates.
Cholinephosphotransferase (
CPT) is the terminal
enzyme for the de novo biosynthesis of PC. We have addressed here whether
Ro5-4864 facilitates some
cancer causing mechanisms in
breast cancer. We report that cell proliferation increases exponentially in aggressive
breast cancer cell lines 11-9-1-4 and BT-549 when treated with nanomolar concentrations of
Ro5-4864. This increase is seen within 24 h of treatment, consistent with the cell doubling time in these cells.
Ro5-4864 also upregulates c-fos expression in
breast cancer cell lines 11-9-1-4 and BT-549, while expression in non-tumorigenic cell line MCF-12A was either basal or slightly downregulated. We further examined the expression of the
CPT gene in
breast cancer (11-9-1-4, BT-549) and non-tumorigenic cell lines (MCF-12A, MCF-12F). We found that the
CPT gene is overexpressed in
breast cancer cell lines compared to the non-tumorigenic cell lines. Furthermore, the activity of
CPT in forming PC is increased in the
breast cancer cell lines cultured for 24 h. Additionally, we examined the
CPT activity in the presence of nanomolar concentrations of
Ro5-4864. Biosynthesis of PC was increased in
breast cancer cell lines upon treatment. We therefore propose that
Ro5-4864 facilitates PC formation, a process important in membrane biogenesis for proliferating cells.