gms | German Medical Science

Objectives: PTEN (Phosphat and tensin homologue deleted on chromosome 10) has been shown to be inactivated in a wide variety of cancers. The role of this gene as a tumor suppressor has been well established. PTEN plays a pivotal role in apoptosis, cell cycle arrest, and possibly cell migration.The aim of the study was to examine the effect of inhibitors of the receptor-tyrosine kinase pathways on apoptosis of human cancer cell lines with different PTEN status.

Methods: Breast cancer cells (BT-474, MCF-7 and MDA-MB-231), ovarian cancer cells (BG-1 and SK-OV-3) and endometrial cancer cells (Ishikawa and HEC-1A) were treated with either 4-OH-Tamoxifen (4-OH-Tam), MEK-inhibitors (PD 98059, U0126), MAPK-inhibitors (PD 169,316, (SB 202190), and HER-family inhibitors (ZD 1839, Trastuzumab). After 18 hours of incubation, apoptosis was measured by cell death detection ELISA. Expression of PTEN was determined by western blot analysis.

Results: BG-1 and BT-474, HEC-1A and MCF-7 cells showed high expression of PTEN, whereas only low expression was detected in MDA-MB-231 and SKOV-3. No expression of PTEN could be seen in Ishikawa cells. Apoptosis could be induced in BG-1, BT-474, MCF-7 and HEC-1A after treatment with different inhibitors of tyrosine kinases. No effect was seen after treatment with SB 202190 in those cells. In MDA-MB 231, SK-OV-3 and Ishikawa cells apoptosis could not be induced.

Conclusions: Our data indicated, that treatment with inhibitors of receptor tyrosine kinase pathways is able to induce apoptosis in cancer cells with high PTEN expression. This effect could not be seen in cancer cells with low PTEN expression.