TY - JOUR
T1 - Control of cyclin D1 expression by antisense oligonucleotides in three ovarian cancer cell lines
AU - Cagnoli, Monica
AU - Barbieri, Federica
AU - Bruzzo, Cristina
AU - Alama, Angela
PY - 1998/9
Y1 - 1998/9
N2 - Cyclin D1 is a critical gene controlling the G1 phase progression through the cell cycle. Alterations of cyclin D1 have been demonstrated in a variety of cancer types. We recently reported that increased cyclin D1 expression is associated with malignancy also in ovarian tumors. Three human ovarian cancer cell lines (SW626, OVCAR-3, IGROV1), expressing high levels of this gene, were used to investigate the effects induced by antisense oligonucleotides to cyclin D1 as antiproliferative compounds. Unmodified 18 met oligomers, targeted to the translation start site of the cyclin D1 cDNA, were able to inhibit the growth of the three cell lines after a single administration of 40 μM. The pattern of cell number reduction ranged between 30 and 55% after 48 h of treatment. Moreover, by RT-PCR and Western blotting, a marked decrease of the cyclin D1 transcript and protein (up to 77% in the SW626) was detected after 24 and 48 h, respectively, from antisense exposure. Conversely, no relevant inhibition was reported in the sense-treated cells. The present data confirm the role of cyclin D1 expression in the proliferative behavior of ovarian cancer and provide additional information that might be helpful in the search for new therapeutic strategies of this disease.
AB - Cyclin D1 is a critical gene controlling the G1 phase progression through the cell cycle. Alterations of cyclin D1 have been demonstrated in a variety of cancer types. We recently reported that increased cyclin D1 expression is associated with malignancy also in ovarian tumors. Three human ovarian cancer cell lines (SW626, OVCAR-3, IGROV1), expressing high levels of this gene, were used to investigate the effects induced by antisense oligonucleotides to cyclin D1 as antiproliferative compounds. Unmodified 18 met oligomers, targeted to the translation start site of the cyclin D1 cDNA, were able to inhibit the growth of the three cell lines after a single administration of 40 μM. The pattern of cell number reduction ranged between 30 and 55% after 48 h of treatment. Moreover, by RT-PCR and Western blotting, a marked decrease of the cyclin D1 transcript and protein (up to 77% in the SW626) was detected after 24 and 48 h, respectively, from antisense exposure. Conversely, no relevant inhibition was reported in the sense-treated cells. The present data confirm the role of cyclin D1 expression in the proliferative behavior of ovarian cancer and provide additional information that might be helpful in the search for new therapeutic strategies of this disease.
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U2 - 10.1006/gyno.1998.5062
DO - 10.1006/gyno.1998.5062
M3 - Article
C2 - 9790790
AN - SCOPUS:0032169680
VL - 70
SP - 372
EP - 377
JO - Gynecologic Oncology
JF - Gynecologic Oncology
SN - 0090-8258
IS - 3
ER -