Regulation of prostate cell collagen receptors by malignant transformation.
Cell adhesion receptors, including the integrin-type collagen receptors (alpha1beta1, alpha2beta1, alpha10beta1 and alpha11beta1) participate in cancer progression and invasion. Quantitative RT-PCR indicated that all 4 receptors are abundantly expressed in sarcoma-derived cell lines, whereas most carcinoma-derived cells express alpha1beta1 and alpha2beta1 only. This was surprising because alpha11beta1 has been connected previously to the progression of lung adenocarcinomas. To test the hypothesis that alpha11 expression may not persist in cultured cancer cells we analyzed fresh tissue samples of 104 total prostatectomies, keeping in mind that prostate cancer cell lines showed negligible alpha11 mRNA levels. In prostate alpha2 expression was significantly lower in poorly differentiated carcinomas when compared to benign lesions (p = 0.0331). In immunohistochemistry the protein levels of alpha2 integrin decreased significantly (p = 0.0001) and the protein levels of alpha11 subunit increased significantly (p = 0.029) with the increasing grade of carcinoma. Thus alpha11beta1 may replace alpha2beta1 during tumor progression. Our observations support the idea that alpha11beta1 may be expressed in tumors but the corresponding cell lines may lose the expression of this integrin. Previous studies have shown that in cell culture androgen receptor (AR) controls alpha2beta1 expression. We measured AR mRNA levels and the number of AR positive nuclei in the prostate samples and the results showed a significant correlation between alpha2beta1 and AR. Androgen receptors may control the mechanisms regulating integrin expression in prostate.
Mirtti
Tuomas
T
Department of Pathology, University of Turku, Turku, Finland. tuomas.mirtti@utu.fi
Nylund
Camilla
C
Lehtonen
Janika
J
Hiekkanen
Heikki
H
Nissinen
Liisa
L
Kallajoki
Markku
M
Alanen
Kalle
K
Gullberg
Donald
D
Heino
Jyrki
J
D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000096:biosynthesis*; D008297:Male; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011944:Receptors, Androgen / Q000502:physiology; D038981:Receptors, Collagen / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology*
D016023:Integrins; D011944:Receptors, Androgen; D038981:Receptors, Collagen; C467800:integrin alpha11beta1