Abstract
Uvomorulin (E-cadherin), a cell adhesion molecule, and Na+,K+-adenosine triphosphatase (ATPase), a marker protein of the basal-lateral cell membrane domains of polarized epithelial cells, were investigated in a group of mouse skin tumors induced by a two-stage chemical carcinogenesis protocol and in cell lines derived from mouse skin papillomas and squamous cell carcinomas (SCC). Although these two markers were present in benign tumors and in non-tumorigenic cell lines, the Na+,K+-ATPase showed an altered pattern of distribution that included the presence of enzyme not only in the basolateral domain but also on the apical domain of the cell membrane of basal and spinous cells in well-differentiated squamous cell carcinomas (SCC). In higher grade SCC, a loss of Na+,K+-ATPase immunoreactivity was simultaneously detected with a marginal or absent expression of uvomorulin. The more differentiated SCC and papillomas expressed less uvomorulin immunoreactivity than normal epidermal cells. Both markers were seen in tumor cell lines that produced well-differentiated SCC after subcutaneous inoculation into nude mice. Neither Na+,K+-ATPase nor uvomorulin could be detected in cell lines that produced high grade, poorly differentiated SCC. Northern blots confirmed the absence of uvomorulin mRNA in these highly malignant cell lines. These data indicate that progression from premalignant papilloma to low-grade SCC and subsequently to high-grade SCC is accompanied by loss of epithelial cell polarity as detected by changes in Na+,K+-ATPase and by decreased or absent expression of uvomorulin in tumors and cell lines characterized by an advanced malignant phenotype.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1179-1185 |
| Number of pages | 7 |
| Journal | American Journal of Pathology |
| Volume | 140 |
| Issue number | 5 |
| State | Published - May 1992 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Alterations in the expression of uvomorulin and Na+,K+-adenosine triphosphatase during mouse skin tumor progression. / Ruggeri, B.; Caamano, J.; Slaga, Thomas J; Conti, C. J.; Nelson, W. J.; Klein-Szanto, A. J P.
In: American Journal of Pathology, Vol. 140, No. 5, 05.1992, p. 1179-1185.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alterations in the expression of uvomorulin and Na+,K+-adenosine triphosphatase during mouse skin tumor progression
AU - Ruggeri, B.
AU - Caamano, J.
AU - Slaga, Thomas J
AU - Conti, C. J.
AU - Nelson, W. J.
AU - Klein-Szanto, A. J P
PY - 1992/5
Y1 - 1992/5
N2 - Uvomorulin (E-cadherin), a cell adhesion molecule, and Na+,K+-adenosine triphosphatase (ATPase), a marker protein of the basal-lateral cell membrane domains of polarized epithelial cells, were investigated in a group of mouse skin tumors induced by a two-stage chemical carcinogenesis protocol and in cell lines derived from mouse skin papillomas and squamous cell carcinomas (SCC). Although these two markers were present in benign tumors and in non-tumorigenic cell lines, the Na+,K+-ATPase showed an altered pattern of distribution that included the presence of enzyme not only in the basolateral domain but also on the apical domain of the cell membrane of basal and spinous cells in well-differentiated squamous cell carcinomas (SCC). In higher grade SCC, a loss of Na+,K+-ATPase immunoreactivity was simultaneously detected with a marginal or absent expression of uvomorulin. The more differentiated SCC and papillomas expressed less uvomorulin immunoreactivity than normal epidermal cells. Both markers were seen in tumor cell lines that produced well-differentiated SCC after subcutaneous inoculation into nude mice. Neither Na+,K+-ATPase nor uvomorulin could be detected in cell lines that produced high grade, poorly differentiated SCC. Northern blots confirmed the absence of uvomorulin mRNA in these highly malignant cell lines. These data indicate that progression from premalignant papilloma to low-grade SCC and subsequently to high-grade SCC is accompanied by loss of epithelial cell polarity as detected by changes in Na+,K+-ATPase and by decreased or absent expression of uvomorulin in tumors and cell lines characterized by an advanced malignant phenotype.
AB - Uvomorulin (E-cadherin), a cell adhesion molecule, and Na+,K+-adenosine triphosphatase (ATPase), a marker protein of the basal-lateral cell membrane domains of polarized epithelial cells, were investigated in a group of mouse skin tumors induced by a two-stage chemical carcinogenesis protocol and in cell lines derived from mouse skin papillomas and squamous cell carcinomas (SCC). Although these two markers were present in benign tumors and in non-tumorigenic cell lines, the Na+,K+-ATPase showed an altered pattern of distribution that included the presence of enzyme not only in the basolateral domain but also on the apical domain of the cell membrane of basal and spinous cells in well-differentiated squamous cell carcinomas (SCC). In higher grade SCC, a loss of Na+,K+-ATPase immunoreactivity was simultaneously detected with a marginal or absent expression of uvomorulin. The more differentiated SCC and papillomas expressed less uvomorulin immunoreactivity than normal epidermal cells. Both markers were seen in tumor cell lines that produced well-differentiated SCC after subcutaneous inoculation into nude mice. Neither Na+,K+-ATPase nor uvomorulin could be detected in cell lines that produced high grade, poorly differentiated SCC. Northern blots confirmed the absence of uvomorulin mRNA in these highly malignant cell lines. These data indicate that progression from premalignant papilloma to low-grade SCC and subsequently to high-grade SCC is accompanied by loss of epithelial cell polarity as detected by changes in Na+,K+-ATPase and by decreased or absent expression of uvomorulin in tumors and cell lines characterized by an advanced malignant phenotype.
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M3 - Article
C2 - 1316085
AN - SCOPUS:0026683589
VL - 140
SP - 1179
EP - 1185
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 5
ER -