Potentiation of Truncated Epidermal Growth Factor-like Receptor on Human Cervical Cancer Cell Line
There has been significant research done on epidermal growth factor receptors
(EGFR) in recent years. Truncations in EGFR been implicated in a varied of
pathologies including malignant neoplasms, such as cancers of the cervix,
breast, ovary, kidney, and lung. Recently, a truncated form of the receptor
(TEGFR) with an approximate weight of 80 kDa has been found in the placenta and
in ovarian cancer. In this study, we show that TEGFR has a potentiation effect
on human cervical cancer cells, HeLa. This effect is seen through addition of
TEGFR to the cultured media and through transient transfection of TEGFR. Both
conditions showed a marked increase in the proliferation of cells compared to
control conditions. This marked increase can be eliminated with the addition of
a PI3K inhibitor. It is our hypothesis that TEGFR controls cell growth by
forming a heterodimer with EGFR, thereby inhibiting its ability to
autophosphorylate. This inhibition confers a conformational change upon EGFR
thereby exposing novel src-2 binding sites. This then allows p85, the
regulatory subdomain of PI3K, to bind and conduct the signal downstream through
existing pathways. This novel pathway could prove to be the regulatory control
mechanism that is responsible for the uncontrollable growth of neoplasms.