Endometrial cancer is the fourth most common female
malignancy in women in developed countries.
Estrogen, and to a lesser degree,
progesterone, regulate specific target genes that are involved in endometrial
tumorigenesis. A family of
proteases involved in cellular proliferation, extracellular matrix degradation and thus, implicated in
tumorigenesis, and regulated by
estrogen and
progesterone in a number of systems, are the
tissue kallikreins (KLKs). KLK4, a new member of the KLK gene family, was found to be expressed to varying levels in a number of
endometrial cancer cell lines- HEC1A, HEC1B, Ishikawa, RL95-2 and KLE- at both the
mRNA and
protein level. On the addition of 10 nmol/L
estradiol,
progesterone, or a combination of both over a 48 h period, an increase in the intracellular
protein levels of K4 were observed when compared to the control (untreated) cells. We have also identified a novel KLK4 transcript with a complete exon 4 deletion. The significance of this alternative transcript, which would give rise to a truncated
protein without a
serine residue (which is essential for catalytic activity), is yet to be established. These cell lines now provide a model system to study the role of KLK4 and the molecular mechanisms of KLK4 regulation by
estrogen and
progesterone, in endometrial
tumorigenesis.