The expression of claudins 1, 2, 3, 4, 5 and 7 was studied in prostate adenocarcinoma and compared to that of non-neoplastic epithelium and Gleason score of the tumors. Additionally, RT-PCR was performed for claudins 2 and 5 in three cases. Strong immunoreactivity of claudins 1, 3, 4 and 7 was seen in prostate adenocarcinoma while expression of claudins 2 and 5 was weaker. In relation to non-neoplastic glands, expression of claudins 2 and 5 was diminished. There was a significant association between the Gleason score and claudin 1 and 5 expression, these claudins were more strongly expressed in tumours with a lower Gleason score. A combined lowered claudin expression was associated with a high Gleason score and a poor prognosis. According to the results, there is a strong claudin expression in prostate adenocarcinoma, especially for claudins 3 and 4. In contrast, claudin 2 was low in neoplastic cells compared to non-neoplastic epithelium, suggesting downregulation of synthesis or altered metabolism/ assembly of this protein during carcinoma development. The association of lowered claudin 1 and 5 expression and lowered overall claudin expression with tumours of a higher Gleason score suggest that claudins may modulate the histologic features of these tumors and in this way influence their biological behaviour.

Acetyl-CoA synthetase (AceCS) provides acetyl-CoA for different physiological processes, such as fatty acid and cholesterol synthesis, as well as the citric acid cycle. We show here that the cytosolic isoform of this enzyme, AceCS1, is expressed during mouse development. In the embryonic stage E9.5 AceCS1 transcripts localize in the cephalic region. At E10.5 the cephalic expression intensifies and transcripts appear also in the spinal cord and in the dorsal root ganglions. During organogenesis AceCS1 is expressed in the liver from E11.5. The AceCS1 gene is expressed also in the testes from E12.5 onwards and expression localizes in the interstitial Leydig cells. In the ovaries, expression is transient and AceCS1 transcripts are detected from E13.5 to E15.5 in the ovarian interstitial component. In the kidneys AceCS1 transcripts appear in a subset of the renal tubules at E16.5 and remains in these structures in newborns. Hence, expression of AceCS1 is developmentally regulated suggesting a role for AceCS1 during embryogenesis.

No abstract

Abstract. Myosin VI, one of the so-called unconventional myosins, is an actin-based molecular motor involved in intracellular vesicle and organelle transport. In human prostate, myosin VI is expressed in prostate epithelium. We examined the effect of myosin VI downregulation in the LNCaP human prostate cancer cell line using an RNA interference approach. Further, the expression of myosin VI in human prostate tissue was examined using immunohistochemistry. The expression of androgen receptor (AR) and E-cadherin was examined in myosin VI knocked-down cells and control cells. We determined 3 H-testosterone uptake in the myosin knocked-down LNCaP cells. Next, we cotransfected LNCaP cells with the myosin VI-specific small interfering RNA (siRNA) duplex and an androgen-responsive luciferase reporter construct and then measured luciferase activity after androgen induction. To clarify whether myosin VI and the AR are interacting proteins, we performed immunoprecipitation studies using myosin VI and AR polyclonal antibodies in androgeninduced LNCaP cells. We confirmed previous results of myosin VI overexpression in human prostate cancer tissue, as in some cases malignant epithelium was more intensively stained than benign epithelium. We found that the expression of AR decreased as a result of myosin VI knock-down. Decreased myosin VI levels did not significantly influence the testosterone uptake of the LNCaP cell line. Instead, we noted a decreased activity of the androgen-regulated mouse mammary tumor virus promoter-reporter vector construct in LNCaP cells cotransfected with myosin VI siRNA duplexes. Finally, we detected the interaction between AR and myosin VI by immunoprecipitation. We propose that myosin VI is a modulator of androgen-dependent gene transcription via interaction with the AR. Thus, myosin VI is a potential therapeutic target for prostate cancer as it could be used as a modulator of AR-dependent gene expression.