Studies on proteins and genes expressed in male accessory sex glands
Principal investigator; Lundwall, Åke, Professor, PhD
Co-workers: Camilla Valtonen-André, Junior consultant
The primary aim of our research is to elucidate the role of seminal plasma proteins with respect to male fertility and prostate cancer. Most of these proteins are synthesized and secreted by accessory sex glands, of which the seminal vesicles and the prostate are by far the most important. Earlier studies showed that many seminal plasma proteins are subjected to a rapid and remarkable evolution - presumably reflecting their biological function. Molecular evolution and expression is therefore a common topic of our investigations. Presently we are studying four proteins/protein families; kallikrein-related peptidases (KLK), beta-microseminoprotein (MSMB), semenogelins and related semen coagulum proteins, and WFDC-type proteinase inhibitors originating from a locus on chromosome 20.
Studies on KLK are presently focused on KLK2, KLK3 (PSA), KLK4 and KLK15, which are investigated in relation to prostate and ovarian cancer. A novel protein that is highly expressed in a prostate cancer cell line was discovered due to its similarity to MSMB. The function of the novel protein, PC3-secreted microprotein (PSMP), is now addressed by way of knock out mice. Functional studies on semenogelins are done in order to evaluate their role as extracellular regulators of Zn(II). Phylogenetic studies show that semenogelin I and II can evolve by gene conversion and not only by duplications and point mutations as previously thought. Protein products of WFDC genes are produced in a variety of expression systems. The recombinant proteins regulatory effect is studied with a panel of serine peptidases and their antibacterial activity is evaluated with cultures of different bacterial strains.
The basic research conducted by our group will give rise to a deeper knowledge about molecules of importance for male reproductive function. This may lead to novel regimes in order to treat involuntary childless couples. Our research may also have an impact on other research fields, e.g. in prostate cancer by providing new molecular tools for diagnosis.
Link to project homepage: http://
5 recent original publications
Lundwall Åke, Clauss Adam
Genes encoding WFDC- and Kunitz-type protease inhibitor domains: are they related?
Biochemical Society transactions. 2011; 39: 1398 - 1402
Clauss A, Lilja H & Lundwall Å
A locus on chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein.
Biochem. J.. 2002; 368: 233-242
Valtonen-André C, Bjartell A, Hellsten R, Lilja H, Härkönen P & Lundwall Å
A highly conserved protein secreted by the prostate cancer cell line PC-3 is expressed in benign and malignant prostate tissue
Biol. Chem.. 2007; 388: 289-295
Lundwall Å, Malm J, Clauss A, Valtonen-André C and Olsson AY
Molecular cloning of cDNA encoding mouse seminal vesicle-secreted protein SVS I and demonstration of homology with copper amine oxidases.
Biol Reprod. 2003; 69: 1923-1930
Olsson AY, Lilja H & Lundwall Å
Taxon-specific evolution of glandular kallikrein genes and identification of a progenitor of prostate-specific antigen.
Genomics. 2004; 84: 147-156
Further publications here (new window)
|Total financing:||1.5 MSEK||Gov grant for clinical research ("ALF"):||0.0 MSEK|
|Total external financing:||0.4 MSEK||Natl and intl prioritized grants:||0.0 MSEK|