RELATIONSHIP OF HSP27 AND ESTROGEN-RECEPTOR IN HORMONE-SENSITIVE AND INSENSITIVE CELL-LINES

A 27 kDa heat shock (HSP27) has been analysed by immunoassay and immun oblotting in oestradiol sensitive and insensitive cells. Oestradiol gr owth responsive MCF7 and T47D human breast cancer cells and growth unr esponsive variants derived therefrom have unaltered levels of HSP27 as well as retaining their oestradiol receptor phenotype. MCF7 cells ind uced to become doxorubicin resistant in culture lose both HSP27 and oe stradiol receptor. Thus, in these three pairs of cells, HSP27 content parallels oestradiol receptor (ER). Analysis of a range of ER positive and negative human cell lines supports the positive relationship betw een HSP27 and ER. This included six ER positive and two ER negative br east tumour lines, one ER positive and one ER negative endometrial tum our cell line and seven ER negative human lines from other sites. One ER negative osteosarcoma line (HTB96) had appreciable levels of HSP27 that were unaffected after stable transfunction with an ER cDNA. Heat shock increases HSP27 levels in some but not all cell lines tested, th e effect being inversely proportional to the basal (37-degrees-C) cont ent. In a mouse mammary tumour cell line, loss of androgen sensitivity was accompanied by loss of HSP27. Loss of HSP27 occurred in MCF7 cell s made drug resistant to Novatrone, vincristine and etoposide as well as doxorubicin; no detectable change was seen in cells made resistant by 5 fluorouracil or X-irradiation. In ER positive ZR75 human breast t umour cells and in both ER negative and positive variants of the HTB96 human osteosarcoma line, the intracellular distribution of HSP27 was analysed. Over 96% of the HSP27 was in the cytosol fraction and the di stribution was unaffected by incubation with oestradiol. HSP27 has bee n discussed in the literature under three different names p29, p24 and HSP27. The data presented in this paper are reviewed in the context o f the previous data. It is concluded that there is a good but not abso lute correlation between the presence of ER and high amounts of HSP27 but that low amounts of HSP27 are present in many ER negative cells. T he correlations between HSP27 and drug resistance are more complex.