Kallikrein 4 (KLK4), a new member of the human kallikrein gene family is upregulated by estrogen and progesterone in the human endometrial cancer cell line, KLE.

Endometrial cancer is the fourth most common female malignancy in women in developed countries. Estrogen, and to a lesser degree, progesterone, regula te specific target genes that are involved in endometrial tumorigenesis. A family of proteases involved in cellular proliferation, extracellular matri x degradation and thus, implicated in tumorigenesis, and regulated by estro gen and progesterone in a number of systems, are the tissue kallikreins (KL Ks.). 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, HEC1 B, Ishikawa, RL95-2 and KLE- at both the mRNA and protein level. On the add ition 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 ob served when compared to the control (untreated) cells. We have also identif ied a novel KLK4 transcript with a complete exon 4 deletion. The significan ce of this alternative transcript, which would give rise to a truncated pro tein without a serine residue (which is essential for catalytic activity), is yet to be established. These cell lines now provide a model system to st udy the role of KLK4 and the molecular mechanisms of KLK4 regulation by est rogen and progesterone, in endometrial tumorigenesis.