Impaired expression and posttranslational processing of connexin43 and downregulation of gap junctional communication in neoplastic human prostate cells

Hossain, Mohammad Zakir; Jagdale, Ajit B.; Ao, Ping; LeCiel, Cosette; Huang, Ruo‐Pan; Boynton, Alton L.

doi:10.1002/(sici)1097-0045(19990101)38:1<55::aid-pros7>3.0.co;2-4

Cited by 38 publications

(17 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Impaired GJIC and loss of Cx expression have been shown to correlate with neoplastic transformation of several human tissues such as breast (Laird et al, 1999), lung (Ruch et al, 2001), brain (Soroceanu et al, 2001), endometrium (Saito et al, 2001), and prostate (Hossain et al, 1999). Testicular cancer is the most common malignancy of young men (Adami et al, 1994;Forman and Moller, 1994), and an increased risk of this cancer has been reported in the population of infertile men (Moller and Skakkebaek, 1999).…”

Section: Discussionmentioning

confidence: 99%

Impaired Gap Junction Connexin43 in Sertoli Cells of Patients with Secretory Azoospermia: A Marker of Undifferentiated Sertoli Cells

Defamie

Berthaut²,

Mograbi

et al. 2003

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:Gap junctions are intercellular channels formed of connexins (Cx) at appositional plasma membranes between adjacent cells that have been involved in the control of cell proliferation and differentiation. Altered Cx expression is implicated consistently in several human diseases and in tumorigenesis. Although Cx43 plays a critical role in Sertoli cell control of spermatogenesis, there is no evidence of its altered expression in human testicular pathologies. We show here that Cx43 mRNA expression was significantly reduced in testes of infertile patients with secretory azoospermia (p Ͻ 0.05) compared with testes displaying normal spermatogenesis (excretory azoospermic patients). In Sertoli cell-only syndrome, in situ hybridization and immunohistochemistry analyses indicated that Cx43 mRNA and protein were undetectable in Sertoli cells but were still present in the interstitial compartment. In a rat model of Sertoli cell-only syndrome, the lack of Cx43 in Sertoli cells was associated with an impairment of gap junction intercellular communication between adjacent Sertoli cells. These results reveal that Cx43 mRNA and protein expression are markedly impaired in Sertoli cells of infertile patients. This defect could be a new functional marker of undifferentiated Sertoli cells and could be related to the increased risk of testicular cancer recently described in the population of infertile men. (Lab Invest 2003, 83:449 -456).

show abstract

Section: Discussionmentioning

confidence: 99%

Impaired Gap Junction Connexin43 in Sertoli Cells of Patients with Secretory Azoospermia: A Marker of Undifferentiated Sertoli Cells

Defamie

Berthaut²,

Mograbi

et al. 2003

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…28 ± 31 These reports present somewhat conflicting data about the connexin status/level of intercellular communication of the cell lines studied in our paper. Mehta et al 29 show that PC -3 is the only cell line that expresses connexin 43 and displays cell ± cell communication, whereas Hossain et al 30 claim that in PC -3 and LNCaP cells, the connexin 43 expression is virtually undetectable. Even though the latter report would better explain our results, it remains difficult to judge as to what is the real connexin status of these cell lines and whether these molecules play any role in the level of the bystander effect of the prostate carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase–mediated suicide gene therapy

et al. 2001

View full text Add to dashboard Cite

To evaluate human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase ( HSV -TK ) ± mediated gene therapy, we tested the utility of different viral vectors on three human cell lines DU -145, LNCaP, and PC -3. Our viral vectors were carrying a fusion gene of HSV -TK and green fluorescent protein for accurate determination of the gene transfer rate and its contribution to the treatment outcome in each case. We observed that adenoviral and lentiviral vectors were efficient vehicles for all the cell lines, whereas Semliki Forest virus and Sindbis virus vectors yielded only a few percent of transgene -positive cells. Despite sufficient gene transfer rates ( 25 ± 45% ) in the ganciclovir ( GCV ) sensitivity experiment, only DU -145 cells were efficiently destroyed under clinically relevant GCV concentrations. This was shown to be due to low level of``bystander effect'' in PC -3 and LNCaP cells. Our data demonstrate that human prostate tumors can be good targets for adenovirus -or lentivirus -mediated HSV -TK / GCV gene therapy, but each tumor should be investigated for gene transfer rate and bystander effect to warrant a sufficient treatment result.

show abstract

“…9 Some studies showed that Cx43 is also a tumour suppressor gene. 1,2,10,11 Several studies also suggest that gap junctional intercellular communication and Cxs contribute to suppression of tumour growth by participating in the regulation of cell death. 9,12 Several studies investigated the role of Cx43 in different carcinomas, 6,9,10 and some studies focused on Cx43 in prostate cancer 1,2,4,7,13 but none on its prognostic role in prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of connexin43 expression in patients with clinically localized prostate cancer

Benkö

Spajić²,

Demirović

et al. 2010

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

Connexins (Cxs) are a family of transmembrane proteins that build cell-to-cell channels in gap junctions. Gap junctions composed of Cxs have an essential role in intercellular communication, adhesion and cell differentiation. Several studies investigated the role of connexin43 (Cx43) in different carcinomas; however, none investigated its prognostic role in prostate cancer. Cx43 expression and relationship with established prognostic features were assessed in a cohort of 102 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma. Cx43 expression in prostate cancer was significantly associated with established features indicative of worse prognosis, such as follow-up time (Po0.001) and preoperative PSA (Po0.007). Patients with lower Cx43 expressions in tumours have shorter follow-up time, which indicated shorter diseasefree survival and higher preoperative PSA values. Furthermore, tumours with positive surgical margins (Po0.001) showed significantly lower Cx43 expression compared with tumours without this feature. In univariate (Po0.001) and multivariate (P ¼ 0.014) analyses, decreased Cx43 expression was found to be a significant predictor of biochemical recurrence free-survival. Study results show the association of decreased Cx43 expression with prostate cancer progression. Moreover, Cx43 could serve as an additional prognostic marker and used together with traditional prognostic markers might help in further stratifying the risk of disease progression in patients with prostate cancer.

show abstract

Impaired expression and posttranslational processing of connexin43 and downregulation of gap junctional communication in neoplastic human prostate cells

Cited by 38 publications

References 21 publications

Impaired Gap Junction Connexin43 in Sertoli Cells of Patients with Secretory Azoospermia: A Marker of Undifferentiated Sertoli Cells

Impaired Gap Junction Connexin43 in Sertoli Cells of Patients with Secretory Azoospermia: A Marker of Undifferentiated Sertoli Cells

Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase–mediated suicide gene therapy

Prognostic value of connexin43 expression in patients with clinically localized prostate cancer

Contact Info

Product

Resources

About