Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Expression of enhancing factor/phospholipase A2 in skin results in abnormal epidermis and increased sensitivity to chemical carcinogenesis

Oncogene volume 22, pages 1936–1944 (2003)Cite this article

Abstract

Enhancing factor (EF), a growth factor modulator, is the mouse homologue of human secretory group II phospholipase A2. EF exhibits growth-promoting activity in vitro, in the presence of epidermal growth factor, and also brings about phenotypic transformation of normal cells. In order to ascertain the role of EF in vivo, a human keratin-14 promoter was used to drive the expression of EF ectopically to squamous epithelial cells. The founder mouse and its progeny showed abnormal whiskers and a scaly, beaded tail. In these mice, keratinization pattern of the epidermis was disturbed and parakeratosis and acanthosis were noted. The transgenic mice, TgK14-EF, expressed EF in the suprabasal layers of tail epidermis as well as in the epithelial cells of hair follicle and sebaceous glands of skin. Expression of EF along with hyperplasia was also observed in other squamous epithelia such as buccal mucosa, tongue and oesophagus. TgK14-EF mice homozygous for the transgene showed delayed and scanty hair growth although the mice were healthy and fertile. The hemizygous TgK14-EF mice were sensitive to a two-stage chemical carcinogenesis and developed a higher number of papillomas than their normal littermates over the course of the experiment. The conversion rate of papilloma to carcinoma was two fold higher in the transgenic mice.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Cohen S and Elliott GA . (1963). J. Invest. Dermatol., 40, 1–5.

  2. Cormier RT, Hong K, Halberg RB, Hawkins TL, Richardson P, Mulherkar R, Dove WF and Lander ES . (1997). Nat. Genet., 17, 88–91.

  3. Deo MG, Mulherkar R and Mane SM . (1983). Ind. J. Biochem. Biophys., 20, 228–230.

  4. Gelb MH, Valentin E, Ghomashchi F, Lazdunski M and Lambeau G . (2000). J. Biol. Chem., 275, 39823–39826.

  5. Grass DS, Felkner RH, Chiang M, Wallace RE, Nevalainen TJ, Bennett CF and Swanson ME . (1996). J. Clin. Invest., 97, 2233–2241.

  6. Green MR, Basketter DA, Couchman JR and Rees DA . (1983). Dev. Biol., 100, 506–512.

  7. Jiang CK, Epstein HS, Tomic M, Freedberg IM and Blumenberg M . (1991). J. Invest. Dermatol., 96, 162–167.

  8. Kadam S and Mulherkar R . (1999). Biochem. J., 340, 237–243.

  9. Kaiser E, Chiba P and Zaky K . (1990). Clin Biochem., 23, 349–370.

  10. Kennedy BP, Payette P, Mudgett J, Vadas P, Pruzanski W, Kwaan M, Tang C, Rancourt DE and Cromlish WA . (1995). J. Biol. Chem., 270, 22378–22385.

  11. Kiguchi K, Bol D, Carbajal S, Beltran L, Moats S, Chan K, Jorcano J and DiGiovanni J . (2000). Oncogene, 19, 4243–4254.

  12. Lavker RM, Miller S, Wilson C, Cotsarelis G, Wei ZG, Yang JS and Sun TT . (1993). J. Invest. Dermatol., 101, 16S–26S.

  13. Morris RJ, Fischer SM and Slaga TJ . (1986). Cancer Res., 46, 3061–3066.

  14. Mulherkar R and Deo MG . (1986). J. Cell. Physiol., 127, 183–188.

  15. Mulherkar R, Desai SJ, Rao RS, Wagle AS and Deo MG . (1991). Histochemistry, 96, 367–370.

  16. Mulherkar R, Rao R, Rao L, Patki V, Chauhan VS and Deo MG . (1993a). FEBS Lett., 317, 263–266.

  17. Mulherkar R, Rao RS, Wagle AS, Patki V and Deo MG . (1993b). Biochem. Biophys. Res. Comm., 195, 1254–1263.

  18. Murakami MY, Nakatani Y, Atsumi G, Inoue K and Kudo I . (1997). Crit. Rev. Immunol., 17, 225–283.

  19. Murillas R, Larcher F, Conti CJ, Santos M, Ullrich A and Jorcano JL . (1995). EMBO J., 14, 5216–5223.

  20. Oshima H, Rochat A, Kedzia C, Kobayashi K and Barrandon Y . (2001). Cell, 104, 233–245.

  21. Roop DR, Krieg TM, Mehrel T, Cheng CK and Yuspa SH . (1988). Cancer Res., 48, 3245–3252.

  22. Shibata MA, Ward JM, Green JE and Merlino G . (1997). Mol Carcinogen, 18, 160–170.

  23. Taylor G, Lehrer MS, Jensen PJ, Sun T and Lavker R . (2000). Cell, 102, 451–461.

  24. Vassar R and Fuchs E . (1991). Genes Dev., 5, 714–727.

  25. Vassar R, Rosenberg M, Ross S, Tyner A and Fuchs E . (1989). Proc. Natl. Acad. Sci. USA, 86, 1563–1567.

  26. Wagle AS, Desai SJ and Deo MG . (1989). Cell Biol. Int. Rep., 13, 309–311.

  27. Xie W, Chow LT, Wu X, Chin E, Paterson AJ and Kudlow JE . (1998). Cell Growth Differ., 9, 313–325.

Download references

Acknowledgements

We thank Dr AS Wagle and Dr RA Bhisey for their helpful discussions and comments on the manuscript; and Mr JK Rane, Mr AV Jadhav, Mr PS Chavan, Mr VM Sakpal and Mr ML Jagtap for their excellent technical assistance. This work was funded partially by the Department of Biotechnology (Grant # BT/R&D/09/034/94), New Delhi. BMK was a recipient of the UGC fellowship, Government of India.

Author information

Authors and Affiliations

  1. Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai, 410208, India

    Rita Mulherkar, Bhakti M Kirtane, Asha Ramchandani, Nirmala P Mansukhani & Sadhana Kannan

  2. Pathology Department, Tata Memorial Hospital, Tata Memorial Centre, Parel, Mumbai, 400012, India

    Kikkeri N Naresh

Authors
  1. Rita Mulherkar
    View author publications

    Search author on:PubMed Google Scholar

  2. Bhakti M Kirtane
    View author publications

    Search author on:PubMed Google Scholar

  3. Asha Ramchandani
    View author publications

    Search author on:PubMed Google Scholar

  4. Nirmala P Mansukhani
    View author publications

    Search author on:PubMed Google Scholar

  5. Sadhana Kannan
    View author publications

    Search author on:PubMed Google Scholar

  6. Kikkeri N Naresh
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Rita Mulherkar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mulherkar, R., Kirtane, B., Ramchandani, A. et al. Expression of enhancing factor/phospholipase A2 in skin results in abnormal epidermis and increased sensitivity to chemical carcinogenesis. Oncogene 22, 1936–1944 (2003). https://doi.org/10.1038/sj.onc.1206229

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.onc.1206229

Keywords

This article is cited by

Search

Advanced search

Quick links