Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study.
BACKGROUND
We compared levels of protein and mRNA expression of three members of the claudin (CLDN) family in malignant breast tumours and benign lesions.


METHODS
Altogether, 56 sections from 52 surgically resected breast specimens were analyzed for CLDN1, CLDN3 and CLDN4 expression by immunohistochemistry. mRNA was also analyzed using real-time PCR in 17 of the 52 cases.


RESULTS
CLDNs were rarely observed exclusively at tight junction structures. CLDN1 was present in the membrane of normal duct cells and in some of the cell membranes from ductal carcinoma in situ, and was frequently observed in eight out of nine areas of apocrine metaplasia, whereas invasive tumours were negative for CLDN1 or it was present in a scattered distribution among such tumour cells (in 36/39 malignant tumours). CLDN3 was present in 49 of the 56 sections and CLDN4 was present in all 56 tissue sections. However, CLDN4 was highly positive in normal epithelial cells and was decreased or absent in 17 out of 21 ductal carcinoma grade 1, in special types of breast carcinoma (mucinous, papillary, tubular) and in areas of apocrine metaplasia. CLDN1 mRNA was downregulated by 12-fold in the sample (tumour) group as compared with the control group using GAPDH as the reference gene. CLDN3 and CLDN4 mRNA exhibited no difference in expression between invasive tumours and surrounding tissue.


CONCLUSIONS
The significant loss of CLDN1 protein in breast cancer cells suggests that CLDN1 may play a role in invasion and metastasis. The loss of CLDN4 expression in areas of apocrine metaplasia and in the majority of grade 1 invasive carcinomas also suggests a particular role for this protein in mammary glandular cell differentiation and carcinogenesis.
Tokés
Anna-Mária
AM
2nd Department of Pathology, Semmelweis University, Budapest, Hungary. ta@korb2.sote.hu
Kulka
Janina
J
Paku
Sándor
S
Szik
Agnes
A
Páska
Csilla
C
Novák
Pál Kaposi
PK
Szilák
László
L
Kiss
András
A
Bögi
Krisztina
K
Schaff
Zsuzsa
Z
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001941:Breast Diseases / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002454:Cell Differentiation; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000502:physiology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D019108:Tight Junctions
C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D008565:Membrane Proteins; D012333:RNA, Messenger
Eur J Cell Biol. 1999 Dec;78(12):849-55
10669103
J Biol Chem. 2001 Dec 21;276(51):48350-5
11602598
Gastroenterology. 2001 Feb;120(2):411-22
11159882
J Cell Biol. 2002 Mar 18;156(6):1099-111
11889141
J Cell Physiol. 2002 Apr;191(1):60-8
11920682
Oncol Res. 2001;12(11-12):469-76
11939410
Nucleic Acids Res. 2002 May 1;30(9):e36
11972351
Prog Biophys Mol Biol. 2003 Jan;81(1):1-44
12475568
Oncogene. 2003 Apr 3;22(13):2021-33
12673207
Int J Mol Med. 2003 Jun;11(6):683-9
12736707
Am J Respir Cell Mol Biol. 2003 Jul;29(1):62-70
12600828
Arch Androl. 2003 Jul-Aug;49(4):271-9
12851029
Clin Cancer Res. 2003 Jul;9(7):2567-75
12855632
Cancer Res. 2003 Oct 1;63(19):6265-71
14559813
J Cell Sci. 1979 Feb;35:393-402
422677
FEBS Lett. 1987 Sep 14;221(2):359-64
3114004
Histopathology. 1991 Nov;19(5):403-10
1757079
J Cell Physiol. 1992 Jul;152(1):35-47
1618921
J Cell Biol. 1998 Apr 20;141(2):397-408
9548718
J Cell Biol. 1998 Jun 29;141(7):1539-50
9647647
J Cell Biol. 1998 Oct 19;143(2):391-401
9786950
Gene. 1999 Jan 21;226(2):285-95
9931503
Trends Cell Biol. 1999 Jul;9(7):268-73
10370242
Carcinogenesis. 1999 Aug;20(8):1425-31
10426787
Curr Biol. 1999 Sep 23;9(18):1035-8
10508613
J Cell Biol. 1999 Oct 4;147(1):195-204
10508866
Am J Physiol Gastrointest Liver Physiol. 2000 Aug;279(2):G250-4
10915631
Hum Genet. 2000 Sep;107(3):249-56
11071387
Cancer Res. 2000 Nov 15;60(22):6281-7
11103784
Endocrinology. 2001 Feb;142(2):854-63
11159859
J Clin Invest. 2001 May;107(10):1319-27
11375422
Clin Chem Lab Med. 2000 Feb;38(2):171-7
10834406